HK1125577B - Treatment of duchenne muscular dystrophy - Google Patents
Treatment of duchenne muscular dystrophy Download PDFInfo
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Abstract
There are disclosed compound of Formula (1): A1, A2, A3 and A4 which may be the same or different, represent N or CR1, X is a divalent group selected from O, S(O)n, C=W, NR4, NC(=O)R5 and CR6R7, W is O, S, NR20, Y is N or CR8, one of R4, R5, R6, R8, R9 and NR20 represents - L -R3, in which L is a single bond or a linker group, additionally, R1, R3 - R9, which may be the same or different, independently represent hydrogen or a substituent and R20 represents hydrogen, hydroxyl, alkyl optionally substituted by aryl, alkoxy optionally substituted by aryl, aryl, CN, optionally substituted alkoxy, optionally substituted aryloxy, optionally substitute alkanoyl, optionally substituted aroyl, NO2, NR30R31, in which R30 and R31, which may be the same or different, represent hydrogen, optionally substituted alkyl or optionally substituted aryl; additionally, one of R30 and R31 may represent optionally substituted alkanoyl or optionally substituted aroyl, n represents an integer from 0 to 2, in addition, when an adjacent pair of A1 - A4 each represent CR1, then the adjacent carbon atoms, together with their substituents may form a ring B, when X is CR6R7, R6 and R7, together with the carbon atom to which they are attached may form a ring C, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the therapeutic and/or prophylactic treatment of Duchenne muscular dystrophy, Becker muscular dystrophy or cachexia.
Description
The present invention relates to a method of treating duchenne muscular dystrophy.
Duchenne Muscular Dystrophy (DMD) is a common inherited neuromuscular disease associated with progressive deterioration of muscle function, first documented by the neurologist Duchenne deboulogen of france 150 years ago, and subsequently named after its name. DMD is characterized by an X-linked recessive genetic disease that affects 3500 males through mutations in the dystrophin gene. The gene is the largest gene in the human genome and comprises 2.6 million DNA base pairs and 79 exons. Approximately 60% of dystrophin mutations are large insertions or deletions that cause a shift in the error stream, of which approximately 40% are genetic point mutations or small shift rearrangements. The vast majority of DMD patients lack dystrophin. Becker muscular dystrophy is a milder type of DMD caused by a decrease in the amount or change in size of dystrophins. The high incidence of DMD (one in ten thousandth of sperm or egg cells) means that genetic screening does not eliminate the disease, and thus an effective therapeutic approach is urgently needed.
There are many animal models of natural and artificial DMD and provide the main basis for preclinical studies (almamand, V. & Campbell, k.p. animal models for Duchenne breast analysis: variable tools for the severity of therapeutics hum. mol. gene. 9, 2459 (2000)). Although mouse, cat and dog animal models have mutations in the DMD gene and show biochemical dystrophinopathy similar to that of humans, their phenotypes show surprising considerable changes. The canine (golden retriever duchenne muscular dystrophy and german short hair instruction retriever) model is similar to humans with a distinct phenotype. These dogs often die of heart failure. Dogs provide the best phenocopy for human disease and are considered a high baseline model for preclinical studies. Unfortunately, raising these animals is very expensive and difficult, and the clinical time course in litters varies.
Mdx mice are most widely used due to their practicality, short gestational and maturation periods, and relatively low cost (Bulfield, g., siler, w.g., light, p.a. & Moore, k.j.xchromosome-linked Duchenne molecular dynamics (mdx) in the mouse, proc.natl acad.sci.usa 81, 1189-.
Since the discovery of the DMD gene about 20 years ago, there has been varying degrees of success in preclinical animal studies to treat DMD, some of which have also been demonstrated in humans. Current treatment methods are broadly divided into three groups: first, methods of gene therapy; second, cell therapy; and third, pharmacological treatment. The main advantage of gene and cell based therapies is the avoidance of the need to correct side effects/conditions (e.g. contractures), respectively, especially at the early stages of the disease. Unfortunately, these approaches face a number of technical hurdles. In addition to toxicity, it has been reported that the immune response of antiviral vectors, myoblasts and recently synthesized dystrophins lacks stable expression and is difficult to deliver.
Pharmacological approaches to the treatment of muscular dystrophy, unlike gene and cell based approaches, are not designed to deliver missing genes and/or proteins. Generally, pharmacological approaches improve the phenotype by reducing inflammation, improving calcium balance, and increasing muscle progenitor proliferation or commitment (commitment) with drugs/molecules. The advantage of these methods is that they are easy to deliver systemically and avoid the immune and/or toxicity problems associated with vector and cell therapy. Although studies of corticosteroids and cromolyn sodium to reduce inflammation, dantrolene (dantrolene) to maintain calcium balance, and clenbuterol to increase muscle strength have yielded promising results, these potential treatments have not been shown to be effective in treating DMD.
An alternative pharmacological approach is upregulation therapy. Upregulation therapy is based on increasing the expression of alternative genes to replace defective genes, which is particularly advantageous for increasing the immune response against previously deleted proteins. Up-regulation of Utrophin, an autosomal allotype gene of dystrophin (paralogue), has been proposed as a potential therapy for DMD (Perkins & Davies, neurousul disease, S1: S78-S89(2002), Khuran & Davies, Nat Rev Drug disease 2: 379-. When utrophin is overexpressed in genetically modified mdx mice, utrophin localizes to the sarcolemma of muscle cells and restores the components of the dystrophin-related protein complex (DAPC), which prevents the development of malnutrition and, correspondingly, leads to improved skeletal muscle function. It has been shown that adenoviral delivery of utrophin in dogs prevents disease. In a murine model, it is effective to increase the expression of utrophin immediately after birth, and no toxicity is found when utrophin is ubiquitously expressed, promising the application of this method to humans. Utrophin is upregulated to a sufficient level to reduce disease by delivering small diffusible compounds.
In a previous screen we have found a group of compounds that upregulate endogenous utrophin and are therefore useful in the treatment of DMD.
According to the present invention we provide the use of a compound of formula I, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prevention of duchenne muscular dystrophy, becker muscular dystrophy or cachexia:
wherein:
A1、A2、A3and A4May be the same or different and represents N or CR1，
X is selected from O, S (O)n、C＝W、NR4、NC(＝O)R5And CR6R7The divalent group of (a) is,
w is O, S, NR20，
Y is N or CR8，
R4、R5、R6、R8、R9And NR20One of them represents-L-R3Wherein L is a single bond or a linker group,
in addition, R3-R9May be the same or different and independently represent hydrogen or a substituent, an
R20Represents hydrogen, hydroxy, alkyl optionally substituted by aryl, alkoxy optionally substituted by aryl, CN, alkoxy optionally substituted by aryl, aryloxy optionally substituted by alkanoyl, aroyl optionally substituted by NO2、NR30R31Wherein R is30And R31Which may be the same or different, represent hydrogen, optionally substituted alkyl or optionally substituted aryl; in addition, R30And R31One of (a) may represent an optionally substituted alkanoyl group or an optionally substituted aroyl group;
n represents an integer of 0 to 2;
in addition to this, the present invention is,
when each adjacent A1-A4To represent CR1When so, then the adjacent carbon atoms and their substituents together form ring B;
when X is CR6R7When then R is6、R7Together with the carbon atoms to which they are attached form a ring C;
when A is1-A4Is CR1When R is1Representative of COR16，R16Preferably alkoxy or NR10R11。
The compounds of formula I may exist in tautomeric, enantiomeric and diastereomeric forms, all of which are included within the scope of the invention.
Some of the compounds of formula I are novel. According to the present invention we also provide novel compounds of formula I as well as processes for their preparation, compositions containing them and their use as pharmaceuticals.
Some compounds falling within the scope of formula I are known, but not as pharmaceuticals. According to the present invention we claim compounds for use as medicaments, which are known in the art but have not previously been used as medicaments.
All compounds of formula I can be prepared by conventional methods. Methods for preparing heteroaromatic ring systems are well known in the art. Specifically, in Comprehensive Heterocyclic Chemistry, Vol.1 (editor: AR Katritzky, CW Rees), Pergamon Press, Oxford, 1984 and Comprehensive Heterocyclic Chemistry II: a Review of the Litterature 1982-. Other sources of compounds that contribute to the synthesis of the target include March's Advanced Organic Chemistry: reactions, Mechanisms, and Structure, Wiley-Interscience; version 5 (20011, 15 days). Reference is made in particular to the synthesis method discussed in WO 2006/044503.
Some conventional synthetic methods are shown below.
Benzoxazoles of formula I or pharmaceutically acceptable salts thereof can be prepared using compounds of formula II.
Scheme 1
Reaction conditions
i.R9CO2H (or R)9COCl), PPA, heat; or R9COCl, dioxane, microwave, then NaOH
ii.R9COCl, pyridine, Room temperature
TsOH, xylene
iv.R9CO2H, HATU, pyridine, DMF
PPA, heating
vi.HATU，DMF，iPr2Net, alkyl NH2At room temperature
The formation of benzoxazole I can be carried out by a variety of methods, as described above.
For example, the reaction of a compound of formula II and an acyl derivative (e.g., an acid and an acid chloride) is carried out in the presence of an acidic catalyst (e.g., polyphosphoric acid) at a suitable temperature with heating in a suitable solvent. As indicated in step (i) above.
The reaction may be carried out in an aprotic solvent, preferably a polar aprotic solvent such as tetrahydrofuran, at a temperature of from-10 ℃ to +150 ℃. Generally, the reaction can be carried out at reflux temperature of the solvent under normal pressure.
Alternatively, the compound of formula II may be initially combined with an excess of the acyl derivative R9COX (where X is, for example, Cl) reacts to effect acylation on oxygen and nitrogen. This allows, for example, the reaction to be carried out in pyridine at room temperature (step ii). The ring closure is then carried out in a subsequent ring closure step to form the compound of formula II, in which the doubled acylated product is heated in xylene in the presence of an acidic catalyst (e.g. sulphuric acid) (step iii).
Another exemplary preparation of the compound of formula I is shown in steps iv and v. First, the amine is coupled to the acid with a peptide coupling agent. Suitable coupling agents are well known in the art and include HBTU, TBTU and HATU. The amino compound is formed in the presence of a suitable coupling agent, for example in DMF in the presence of a nucleophilic catalyst such as pyridine.
When R is1＝CO2H, the acid may be coupled with an amine as shown in step (vi). Suitable coupling conditions include at room temperature,1Pr2NEt，R16NH2In the presence ofHATU was used in DMF.
Among them, compounds in which the six-membered ring is substituted with an amine derivative are particularly advantageous. They can be prepared using the intermediate amine derivatives III.
Scheme 2
Reaction conditions are as follows:
i. (i) same as scheme 1
ii.R17COCl, pyridine (or NEt)3DCM); or R9CO2H. HATU, pyridine, DMF
(i) same as scheme 1
iv.SnCl2EtOH, heating; or Pd/C, H2IMS; or Fe, NH4Cl, IMS/water, heating
v.R9NCO, DCM, Room temperature
vi.NaBH(OAc)3、R10CHO, DCE, Room temperature
vii.R14SO2Cl, pyridine, DCM, room temperature
The intermediate amine III may be obtained by step (i) of the process shown in scheme 1 (wherein R is1＝NH2) Or synthesized using a two-step process as defined in steps (iii) and (iv) of scheme 2. Nitro-substituted benzoxazole derivatives V are prepared from nitro-substituted phenyl derivatives IV by a similar procedure as shown in step 1 of scheme 1, and the nitro-benzoxazole derivatives V are then reduced in a subsequent step to give intermediate amines III. Suitable methods for reducing the nitro group to give the amine are known to those skilled in the art. Adding NO2Reduction to NH2The selective method of (A) comprises using Sn/HCl or H in a suitable solvent such as ethanol at a temperature of 0-80 deg.C2Pd/C, or heating industrial methanol denatured wine in the presence of ironNH in concentrate/Water4Cl。
The intermediate amine III is then coupled as desired.
The amide derivatives of formula IV can be prepared by coupling an amine III with an acyl derivative. This may be achieved, for example, by the use of pyridine or CH2Cl2(step ii) by reacting a suitable acid chloride.
Sulfonamide derivatives VII can be obtained, for example, by reacting amines III with CH at room temperature in the presence of pyridine2Cl2By reaction of the appropriate sulfonyl chloride.
The amine derivative VIII is prepared by using a suitable reductive amination strategy. Reductive amination is a method well known in the art. These include, for example, reacting an amine with a suitable aldehyde, sodium triacetoxyborohydride in 1, 2-dichloroethane.
Urea derivatives of the formula IX can be prepared, for example, by reacting the amines III with suitable isocyanates at CH at room temperature2Cl2The preparation method is as follows.
The benzothiazole of formula X or a pharmaceutically acceptable salt thereof may be prepared with a compound of formula XI.
Scheme 3
Reaction conditions are as follows:
i.R9COCl, pyridine, Room temperature
ii.Na2S，S8IMS, heating
iii.Fe，NH4Cl, IMS, heating
iv.R17COCl, pyridine (or NEt)3DCM); or R17CO2H, HATU, pyridine, DMF
The compound of formula XI may be converted into the corresponding amide compound, for example by reaction with a suitable acid chloride in pyridine (step (i)) or with a suitable peptide coupling agent. As mentioned above, these methods are well known to those skilled in the art.
The amide compound is then reacted with Na in industrial methanol denatured alcohol under elevated temperature conditions2S、S8To form the nitrobenzothiazole of formula XII. As previously described, nitro derivative XII may be reduced and the resulting primary amine treated in a manner similar to the treatment of primary amines in steps (ii), (v), (vi) and (vii) of scheme 2.
Scheme 4
Reaction conditions are as follows:
i.R9CO2h, PPA, heating; or R9COCl, pyridine; then PPA is heated
ii.SnCl2IMS, heating; or Pd/C, H2，IMS
iii.R17COCl, pyridine, etc. (see scheme 1)
iv.R4NH2DMSO, alkali, heat
Sodium dithionite, THF/water; see also (ii)
Benzimidazoles of formula XII can be prepared according to scheme 4. The diaminophenyl derivative of formula XIII is reacted with an acyl derivative (e.g., an acid or acid chloride) in the presence of an acidic catalyst (e.g., polyphosphoric acid) at a suitable temperature in a suitable solvent to produce the benzimidazole derivative of formula XII. This is step (i) as described above. The nitro group is then reduced and manipulated as described above to provide the other functional group.
Alternatively, benzimidazoles may be prepared by reacting a dinitro compound of formula XIV, wherein X represents a leaving group, preferably a halogen, such as chlorine or fluorine, with an amine in DMSO at elevated temperature and in the presence of a base. Subsequent selective reduction of the nitro group in THF/water was carried out by using sodium dithionite to give the diamine of formula XV. Ring closure to form benzimidazole and processing of nitro group was performed as described above.
Scheme 5
Reaction conditions are as follows:
i.Na2s hydrate, MeOH, NH4Cl, water; or Na2S2O4EtOH; or SnCl2，EtOH
ii as in scheme 1 (i); or R9COCl, pyridine; then PPA is heated
iii.SnCl2EtOH, heating
iv.R1B(OH)2，Pd(PPh3)4，K2CO3Dioxane/water, microwave
v.R17COCl, pyridine, Room temperature
EtOC (S) SK, pyridine, heating
vii.SOCl2(ii) a Or POCl3
viii.R3B(OH)2，Pd(PPh3)4，K2CO3Solvent(s)
ix.PPA，R2CO2H heating
Benzoxazoles of formula XVI can be prepared by analogous methods as discussed above. For example, the process shown in (ix) above comprises heating a compound of formula XVII and a suitable acyl derivative, such as a carboxylic acid, in a suitable solvent in the presence of an acid catalyst.
Benzoxazoles of formulas XVIII and XIX may be synthesized using suitable nitro compounds of formula XX. Reduction of the nitro compound of formula XX affords the corresponding amino alcohol XXI (e.g., using Sn/HCl or other suitable methods known to those of ordinary skill in the art). The formation of benzoxazoles by reaction of an amino alcohol with a suitable acyl derivative can be achieved by any of the methods described above.
For oxazoles of formula XXIII, where X ═ Br, then further derivatives can be obtained using Suzuki coupling reactions. An example of a suitable condition is R1B(OH)2、Pd(PPh3)4、K2CO3Dioxane/water, microwave, wherein the benzoxazole of formula XIX is obtained. Those skilled in the art are familiar with Suzuki coupling reactions and can readily obtain a variety of compounds by controlling the conditions.
(iii) for the oxazole obtained by step (ii), wherein X ═ NO2The nitro group can be reduced to the corresponding amine by the methods described above, which are well known to those skilled in the art. The amine is then converted to the compound of formula XVIII using the procedures discussed in scheme 2.
Alternatively, benzoxazoles of formula XVIII can also be prepared from compounds of formula XX by thiocarbamate XXII, which is prepared by heating a compound of formula XX in pyridine and etoc(s) SK. With known reagents, e.g. SOCl2Or POCl3The compound of formula XXII is converted to the chloride of formula XXIII. The benzoxazole of formula XVIII is obtained from a Suzuki coupling reaction using the conditions of step viii above.
In the above processes, it may be necessary to protect functional groups, such as hydroxyl or amino groups, present in the starting material, and it may be necessary to remove one or more of the protecting groups to give compounds of formula I.
Suitable protecting Groups and methods for their removal are described, for example, in "Protective Groups in Organic Synthesis" by T.Greene and P.G.M.Wutts, John Wiley and Sons Inc., 1991. The hydroxyl group may be protected, for example, with the following groups: arylmethyl groups such as benzyl, biphenylmethyl, or trityl; acyl such as acetyl, trichloroacetyl or trifluoroacetyl; or a tetrahydropyran derivative. Suitable amino protecting groups include: arylmethyl groups such as benzyl, (R, S) - α -phenylethyl, biphenylmethyl, or trityl; acyl, such as acetyl, trichloroacetyl or trifluoroacetyl. Commonly used deprotection methods include hydrogenolysis, acid or base hydrolysis, or photolysis. The arylmethyl groups can be removed, for example, by hydrogenolysis in the presence of a metal catalyst such as palladium on charcoal. The tetrahydropyranyl group may be removed by hydrolysis under acidic conditions. The acyl group may be removed by hydrolysis in the presence of a base such as sodium hydroxide or potassium carbonate, or a group such as trichloroacetyl group may be removed by reduction with zinc and acetic acid.
The compounds of formula I and salts thereof may be isolated from their reaction using conventional techniques.
Salts of the compounds of formula I may be formed by reacting the free acid or salt thereof, the free base or salt or derivative thereof with one or more equivalent amounts of a suitable base or acid. The reaction may be carried out in a solvent or medium in which the salt is insoluble, or in a solvent in which the salt is soluble, such as ethanol, tetrahydrofuran or diethyl ether, which solvent or medium may be removed in vacuo, or lyophilized. The reaction may also be a metathesis process, or may be carried out on an ion exchange resin.
Pharmaceutically acceptable salts of the compounds of formula I include: alkali metal salts, such as sodium and potassium salts; alkaline earth metal salts, such as calcium and magnesium salts; salts of group III elements, such as aluminum salts; and an ammonium salt; salts with suitable organic bases, such as hydroxylamine, lower alkylamino, such as methylamino or ethylamino; salts with substituted lower alkylamino groups, such as hydroxy-substituted alkylamino; or salts with monocyclic nitrogen heterocycles, such as piperidine or morpholine salts; and salts with amino acids such as arginine, lysine salts, etc., or N-alkyl derivatives thereof; or salts with aminosugars, such as N-methyl-D-glucosamine or glucosamine. Physiologically acceptable non-toxic salts are preferred, although other salts may also be used to isolate or purify the product.
Diastereoisomers may be separated by conventional techniques, such as chromatography or fractional crystallisation. The different optical isomers may be separated by resolution of the racemates or other mixtures of the compounds using conventional techniques, such as fractional crystallization or HPLC techniques. Alternatively, the desired optical isomer may be prepared by carrying out the reaction with a suitable optically active starting material under conditions which do not cause racemization.
Substituents which alkyl groups may represent include methyl, ethyl, butyl such as sec-butyl.
Halogen may represent F, Cl, Br and I, in particular Cl.
In the compound of formula I R3Examples of substituents represented include alkyl, alkoxy or aryl, each optionally substituted with one or more, preferably 1-3 substituents R2Substituted, R2May be the same or different.
Further, when L is a single bond, R3May be a sulfanyl group, which is optionally substituted by an alkyl group or an optionally substituted aryl group,
thioaryl, wherein aryl is optionally substituted,
optionally substituted aryl,
A hydroxyl group(s),
NO2，
CN，
NR10R11，
the halogen(s) are selected from the group consisting of,
SO2R12，
NR13SO2R14，
C(＝W)R16，
OC(＝W)NR10R11，
NR15C(＝W)R17，
P(＝O)OR40R41，
R10、R11、R12、R13、R14、R15、R16、R17、R40and R41Which may be the same or different, represent hydrogen, alkyl optionally substituted with optionally substituted aryl,
in addition to this, the present invention is,
NR10R11together with the nitrogen to which they are attached form a ring,
R12can be mixed with NR10R11In the same way, the first and second,
when R is17Is NR10R11When R is10And R11Which may be the same or different, may be hydrogen, CO alkyl and CO optionally substituted aryl,
R16and R17Which may be the same or different, are each:
an alkyl group substituted with one or more of a halogen, an alkoxy optionally substituted aryl, or an optionally substituted aryl,
an aryloxy group which may be optionally substituted,
aryl radicals or NR10R11，
And when R is16Or R17Is NR10R11When R is10And R11One of which may also be an optionally substituted CO alkyl group or an optionally substituted CO aryl group,
in addition to R17In addition, R16And may also be a hydroxyl group.
Substituent R1And R2Which may be the same or different, examples include:
an alkyl group optionally substituted with one or more halogen, alkoxy, or optionally substituted aryl, thioaryl or aryloxy groups,
alkoxy optionally substituted by alkyl or optionally substituted aryl
A hydroxyl group(s),
O(C＝W)NR10R11，
an optionally substituted aryl group, which is optionally substituted,
a sulfanyl group optionally substituted by an alkyl group or an optionally substituted aryl group
Thioaryl, wherein aryl is optionally substituted,
NO2，
CN，
NR10R11，
the halogen(s) are selected from the group consisting of,
SO2R12，
NR13SO2R14，
C(＝W)R16，
NR15C(＝W)R17，
R10、R11、R12、R13、R14、R15、R16and R17Which may be the same or different, represent hydrogen, optionally substituted aryl optionally substituted alkyl, optionally substituted aryl,
in addition to this, the present invention is,
NR10R11together with the nitrogen to which they are attached form a ring,
R12can be mixed with NR10R11In the same way, the first and second,
when R is17Is NR10R11When R is10And R11Which may be the same or different, may be hydrogen, CO alkyl and CO optionally substituted aryl,
R16may be hydroxy, alkoxy or NR10R11，
R17May be an alkyl group, substituted by one or more halogens, alkoxy groups, optionally substituted aryl groups or NR10R11The substitution is carried out on the raw materials,
when R is17Is NR10R11When is not yet present, NR10R11May be hydrogen, CO alkyl and CO optionally substituted aryl.
When L is a linker group, examples of linker group L include:
O、S、(CO)nNR18，
alkylene, alkenylene, alkynylene, each optionally O, S, NR18Is interrupted by one or more C-C single, double or triple bonds,
-an N-single or double bond,
R18is hydrogen, alkyl, COR16。
When L is (CO)nNR18When n is 0, 1 or 2, R is 1 or 218Hydrogen is preferred.
Although R is4、R5、R6、R7And R8Has a wide variation range, but R4、R5、R6、R7And R8Preferably hydrogen, alkyl or optionally substituted aryl.
Preferably, Y is N, X is O, S or NR4. The compound of formula I is preferably benzoxazole, benzothiazole or benzimidazole.
Although R is4、R6、R8Or R9May be any of-L-R3-, but in preferred compounds R9is-L-R3-。
The alkyl group can be any alkyl chain. Alkyl groups include straight and branched, saturated and unsaturated alkyl groups, and cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Preferably, however, when any substituent is alkyl, the alkyl is saturated, linear or branched and has from 1 to 10 carbon atoms, preferably from 1 to 8 carbon atoms, and particularly preferably from 1 to 6 carbon atoms. When any substituent is alkyl, particularly preferred groups are cycloalkyl groups such as cyclopropyl, cyclobutyl, cycloalkyl, cyclohexyl and cycloheptyl.
The aryl group may be any aromatic system. Preferably, in the compound of formula I, aryl is an aromatic hydrocarbon group, or a 5-to 10-membered aromatic heterocyclic ring containing 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen in addition to carbon atoms. We prefer to have 1 or 2 heteroatoms. The aromatic heterocyclic ring comprises furan, thiophene, pyrrole and pyridine.
Particularly preferably, when the aryl group is an aromatic hydrocarbon group, the aryl group is a 6-to 10-membered monocyclic or bicyclic ring, such as phenyl or naphthyl.
Said saturated or unsaturated heterocyclic rings include those containing 4 to 7 ring atoms, preferably 5 or 6 ring atoms, preferably 1 or 2 heteroatoms selected from N, S and O. The heterocyclic ring includes pyrrolidine, piperidine, tetrahydrofuran, piperazine and morpholine. When NR is10R11When a heterocyclic ring is formed, a nitrogen-containing heterocyclic ring is particularly preferable.
When each adjoining A is as described above1-A4To represent CR1When the carbon atoms adjacent to each other and their substituents may form a ring B together; when X is CR6R7When R is6、R7And the carbon atoms to which they are attached may together form a ring C. Preferably, ring B and/or ring C is a 3-10 membered carbocyclic or heterocyclic ring, saturated or unsaturated.
Particularly preferably, ring B is a benzene ring.
Particularly preferably, ring C is a 3-10 membered saturated or unsaturated carbocyclic ring.
We particularly prefer at least one R in the compound1Is NR15C(＝W)R17Particularly preferably NR15COR17A group.
We also prefer at least one R in the compound1Is CONR10R11。
For a radical in particularly preferred compounds, at least one R1Is an amide group NHCOR17Wherein R is17Selected from:
alkyl radical C1-C6，
Alkyl C substituted by phenyl1-C6，
By alkoxy radicals C1-C6Substituted alkyl radical C1-C6，
Haloalkyl C1-C6，
Perfluoroalkyl radical C1-C6，
Phenyl optionally substituted by one or more halogen, alkyl C1-C6C, alkoxy radical1-C6Amino, (alkyl C)1-C6) Amino, di (alkyl C)1-C6) Substituted by amino or phenyl, or substituted by phenyl,
CH is a CH phenyl group, and the phenyl group,
naphthyl, pyridyl, thiophenyl, and furanyl.
We prefer R in the compound1And R2One or both of which are not-COOH.
For another group of preferred compounds, at least one R1Is NR15CONR10R11Wherein R is10And R11May be the same or different and are selected from optionally substitutedSubstituted aryl, alkyl and optionally substituted CO aryl. In a particularly preferred group, at least one R1Is NHCONHR15，R15Selected from phenyl, C1-C6Alkyl and CO phenyl optionally substituted with one or more halogens.
For another radical of particularly preferred compounds, at least one R1Is C optionally substituted by phenyl or a 5-or 6-membered saturated or unsaturated heterocycle containing 1-2 heteroatoms selected from N, S and O1-C6An alkyl group.
For another radical of particularly preferred compounds, at least one R1Is COR16，R16Is alkoxy C1-C6Amino, (alkyl C)1-C6) Amino or di (alkyl C)1-C6) An amino group.
For another radical of particularly preferred compounds, at least one R1Comprises the following steps:
NO2，
the halogen(s) are selected from the group consisting of,
amino or (alkyl C)1-C6) Amino or di (alkyl C)1-C6) Amino group, wherein alkyl group C1-C6Optionally substituted by phenyl or a 5-or 6-membered saturated or unsaturated heterocycle,
NHSO2alkyl radical C1-C6，NHSO2A phenyl group,
SO2alkyl radical C1-C6，
Optionally is covered with C1-C6Alkoxy C1-C6A substituted phenyl group, which is substituted,
a 5-to 10-membered saturated or unsaturated monocyclic or bicyclic heterocycle containing 1-3 heteroatoms selected from N, S and O.
R3Also vary widely. Preferably, R3Is aryl, optionally substituted by 1-3 substituents R2Substituted, R2May be the same or different.
Particularly preferably, R3Is 5-10 membered aromatic monocyclic or bicyclic ring, especially hydrocarbon 5-10 membered aromatic monocyclic or bicyclic ring such as benzene or naphthalene.
Alternatively, the 5-10 membered aromatic monocyclic or bicyclic ring may be a heterocyclic ring containing up to 3 heteroatoms selected from N, S and O, such as thiophene, furan, pyridine or pyrrole.
Preferably, the substituent R2Selected from:
alkyl radical C1-C6Optionally substituted with thiophenyl or phenoxy, each optionally substituted with halogen,
alkoxy C1-C6，
A phenyl group,
thioaryl radical C1-C6A thiophenyl group, optionally substituted with halogen,
NO2，
CN，
NR10R11wherein R is10And R11May be the same or different and is hydrogen, alkyl C1-C6Or together with the nitrogen atom to which they are attached form a 5-7 membered ring which may contain one or more further heteroatoms selected from N, S and O,
the halogen(s) are selected from the group consisting of,
SO2R12wherein R is12Is a 5-7 membered ring containing one or more additional heteroatoms selected from N, S and O,
NHCOR17wherein R is17Is composed of
Alkyl radical C1-C6Optionally substituted with:
phenyl or halogen, or
Optionally is covered withAlkoxy C1-C6Carboxyl-or halogen-substituted phenyl, or
A 5-or 6-membered saturated or unsaturated heterocyclic ring,
phenyl, or optionally substituted by halogen, alkoxy C1-C6Carboxyl or SO2NR10R11A substituted 5-or 6-membered saturated or unsaturated heterocyclic ring,
particularly preferably, when R is2Is NR10R11When is not yet present, NR10R11Is N-pyrrole, N-piperidine, N' (C)1-C6) Alkyl N-piperazines or N-morpholines.
Preferably, the linker group L is:
-NH.NH-
-CH＝CH
-NCOR16wherein R is16Is phenyl or a 5-or 6-membered saturated or unsaturated heterocycle, optionally substituted by halogen, alkoxy C1-C6And carboxyl substitution.
A1-A4Is N or CR1. Thus, the 6-membered benzoxazole ring may contain 1, 2, 3 or 4 nitrogen atoms. In an embodiment of the invention, A1-A4Two of which are nitrogen, A1-A4One of which is nitrogen, and all of A1-A4Is CR1。
Among the particularly preferred compounds:
A1、A2、A3and A4May be the same or different and is N or CR1，
X is selected from O, S (O)n、C＝W、NR4、NC(＝O)R5And CR6R7The divalent group of (a) is,
w is O, S, NR20，
Y is N or CR8，
R4、R5、R6、R8、R9And NR20One of (A) is-L-R3Wherein L is a single bond or a linker group,
furthermore, R4-R9May be the same or different and are each hydrogen or a substituent, and
R20is hydrogen, hydroxy, alkyl optionally substituted by aryl, alkoxy optionally substituted by aryl, CN, alkoxy optionally substituted, aryloxy optionally substituted, alkanoyl optionally substituted, aroyl optionally substituted, NO2、NR30R31Wherein R is30And R31May be the same or different, is hydrogen, optionally substituted alkyl or optionally substituted aryl; furthermore, R30And R31One of which may be an optionally substituted alkanoyl group or an optionally substituted aroyl group, n is an integer of 0 to 2,
R3is alkyl, alkoxy or aryl, each optionally substituted by 1 to 3 substituents R2Substituted, R2Which may be the same or different from each other,
R1and R2Which may be the same or different, are:
an alkyl group optionally substituted with one or more halogen, alkoxy or optionally substituted aryl, thioaryl or aryloxy groups,
alkoxy optionally substituted with alkyl or optionally substituted aryl,
a hydroxyl group(s),
OC(＝W)NR10R11
an optionally substituted aryl group, which is optionally substituted,
a sulfanyl group, which is optionally substituted by an alkyl group or an optionally substituted aryl group,
thioaryl, wherein aryl is optionally substituted,
NO2，
CN，
NR10R11，
the halogen(s) are selected from the group consisting of,
SO2R12，
NR13SO2R14，
C(＝W)R16，
NR15C(＝W)R17，
R10、R11、R12、R13、R14、R15、R16and R17Which may be the same or different, is hydrogen, alkyl optionally substituted with optionally substituted aryl,
in addition, the method can be used for producing a composite material
NR10R11Together with the nitrogen atom to which they are attached may form a ring,
R12can be mixed with NR10R11In the same way as above, the first and second,
when R is17Is NR10R11When is not yet present, NR10R11Hydrogen, CO alkyl and CO optionally substituted aryl,
R16can be hydroxy, alkoxy or NR10R11，
R17May be alkyl, alkoxy, optionally substituted aryl or NR substituted by one or more halogens10R11，
When R is17Is NR10R11When is not yet present, NR10R11May be hydrogen, CO alkyl and optionally CO substituted aryl,
in addition to this, the present invention is,
when each adjacent A1-A4To represent CR1When the ring B is a ring B, adjacent carbon atoms and substituents thereof may form a ring;
when X is CR6R7When R is6、R7Together with the carbon atoms to which they are attached form a ring C;
or a pharmaceutically acceptable salt thereof,
use in the manufacture of a medicament for the treatment and/or prevention of duchenne muscular dystrophy, becker muscular dystrophy or cachexia.
We also provide a method of treating and/or preventing duchenne muscular dystrophy, becker muscular dystrophy or cachexia in a patient in need thereof, the method comprising administering to the patient an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
The compounds of formula I for the treatment of DMD are generally administered in the form of pharmaceutical compositions.
Thus, the present invention further provides a pharmaceutical composition preferably comprising less than 80% w/w, particularly preferably less than 50% w/w (e.g. 0.1-20%) of a compound of formula I or a pharmaceutically acceptable salt thereof as described above, in admixture with a pharmaceutically acceptable diluent or carrier.
We also provide a process for preparing the pharmaceutical composition containing the mixed ingredients. The pharmaceutical formulations and suitable carriers, diluents which may be used are as follows:
for intravenous injection or infusion-pure water or normal saline;
for inhalation compositions-raw lactose;
for tablets, capsules and dragees-microcrystalline cellulose, calcium phosphate, diatomaceous earth, sugars (such as lactose, glucose or mannitol), mica, stearic acid, starch, sodium bicarbonate and/or gelatine;
for suppositories-natural or hydrogenated oils or waxes.
When the compounds are used in aqueous solutions, such as for injection, it may be necessary to combine other excipients. Of particular note are chelating agents or chelators, antioxidants, tonicity adjusting agents, pH adjusting agents and buffers.
If desired, the solution containing the compound of formula I may be evaporated, for example by lyophilization or spray drying, to provide a solid composition which may be reconstituted prior to use.
When not in solution form, the compounds of formula I are preferably in a form having a mean diameter of the substance of from 0.01 to 10 μm. The compositions may also contain suitable preservatives, stabilisers, wetting agents and solubilisers such as water soluble cellulose polymers (e.g. hydroxypropylmethylcellulose) or water soluble dihydric alcohols (e.g. propylene glycol), sweetening, colouring and flavouring agents. Where appropriate, the compositions may be formulated in sustained release dosage forms.
The amount of the compound of formula I in the pharmaceutical composition is generally about 0.01 to 99.9 wt%, preferably about 0.1 to 50 wt%, relative to the total dosage form.
The dosage of the compound of formula I is determined by considering the age, body weight, general health, diet, time of administration, method of administration, clearance, drug combination, disease level, and other factors of the patient being treated.
The dosage will vary depending on the target disease, condition, subject of administration, method of administration and the like, but for oral therapeutic agents for treating patients with duchenne muscular dystrophy, the dosage is 0.01mg to 10g, preferably 0.1 to 100mg, administered in a single dose or in 2 or 3 portions per day.
The potential activity of compounds of formula I for the treatment of DMD can be demonstrated by the preliminary assays and screens described below.
1. Luciferase reporter Gene detection (murine H2K cells)
The cell line used for the screening was the immortalized mdx murine H2K cell line stably infected with a plasmid containing an approximately 5kb fragment of the utrophin a promoter, which includes the first untranslated exon linked to a luciferase reporter gene (see figure 1).
Under conditions of low temperature and medium containing interferon, the cells remain myoblasts. They were placed in 96-well plates and incubated in the presence of the compound for 3 days. The lysed cells are then assayed for luciferase levels and the light output of the expressed luciferase gene is read using a well plate luminometer.
An example of the pharmacological dose response of a compound in the assay is shown in figure 2.
Mdx mouse
The data obtained from ADMET data were prioritized and the compound with the best in vitro luciferase activity and reasonable ADMET data was prioritized for testing in mdx proof-of-concept studies, where the test results are expressed as whether any of the compounds had the ability to increase utrophin in dystrophin (dystrophin) -deficient muscle when compared to control animals dosed with vehicle alone.
Two animals were injected intraperitoneally daily (ip) with 10mg/kg of compound for 28 days, and were age-matched. Muscle samples were removed and processed for sectioning (to determine the increase in the granulation membrane staining of utrophin) and for immunoblotting (Western blotting to determine the overall increase in utrophin levels).
FIG. 3 shows an example of a TA muscle section stained with a mouse utrophin-specific antibody. The amount of sarcolemma-bound utrophin was shown to be increased compared to mdx mice injected with vehicle alone.
Muscle sections obtained from the above-treated mice were subjected to an immunoblotting treatment and specific antibody staining (refer to fig. 4). The muscles to which CPD-A was administered showed a large increase in the overall level of utrophin in the TA leg muscles and diaphragm. Two mice receiving CPD-a (V2 and V3) showed increased levels of utrophin expression compared to controls.
The positive upregulation data from the first 28-day study was then repeated in two mice for 28 days. A total of three different compounds showed the ability to increase utrophin expression levels in mdx mice in duplicate when injected daily intraperitoneally (ip) for 28 days. This data demonstrates that the compounds are capable of providing a large increase in utrophin levels in mdx muscle when injected intraperitoneally, thus convincing us that this approach would alleviate the disease, since all data obtained to date indicate that a more than three-fold increase in utrophin levels has a large functional effect on dystrophin deficient muscles.
Maintenance of H2K/mdx/Utro A reporter cell line
The H2K/mdx/Utro A reporter cell line was passaged twice weekly until ≦ 30% confluency. Cells were in 10% CO2The growth was carried out at 33 ℃.
To remove myoblasts to adhere, they were cultured in insulin/EDTA until the monolayer began to detach.
Culture medium
DMEM Gibco 41966
20％FCS
1% Pen/Streptococcus mutans
1% glutamate
10ml of chick embryo extract
Interferon (1276905 Roche) was added to fresh 10. mu.l/50 ml medium
Luciferase assay in 96-well plates
H2K/mdx/Utro A reporter cell line cells were seeded into 96-well plates (Falcon353296, opal) at a density of about 5000 cells/well in 190ul of normal medium. The plates were then placed in 10% CO2Incubated at 33 ℃ for 24 hours.
By adding 10ul of diluted compound to each well, the final concentration of compound administered was 10 μ M. The plates were then further incubated for 48 hours.
Cell lysis was performed according to the manufacturer's instructions (Promega Steady-Glo luciferase assay System (E2520)). The cells were then counted for 10 seconds using a microplate illuminometer (Victor 1420).
Compound preservation
Compounds for screening were stored in batches of 10mM in 100% DMSO at-20 ℃ until required.
Injection of mdx mice with Compounds
Mdx was selected from the feeder clones for testing. Mice were injected intraperitoneally daily (ip) with vehicle or 10mg/kg of compound. The mice were weighed and the compounds were diluted in 5% DMSO, 0.1% tween/PBS.
At appropriate time points, the mice were sacrificed by cervical dislocation and the muscles were dissected for analysis.
Muscle analysis
Immunohistochemistry
Tissues for sectioning were dissected, immersed in OCT (Bright Cryo-M-Bed), and frozen on liquid nitrogen-cooled isopentane. Unfixed 8. mu.M cryosections were cut on Bright Cryostat and stored at-80 ℃.
To prepare for staining, sections were blocked in 5% fetal calf serum in PBS. Primary antibodies were diluted in blocking reagent and incubated on the sections for 1.5 hours in humid space, then washed three times in PBS for 5 minutes each. The secondary antibody was also diluted in blocking reagent and then incubated in a dark humid space for 1 hour. Finally, the coverslips were fixed with hydromount three times for 5 minutes each in PBS. The slides were analyzed using a Leica fluorescence microscope.
Results
The biological activity was assessed in murine H2K cells using the luciferase reporter assay, classified as follows:
+ up to 200% relative to control
+ + between 201% and 300% relative to control
Between 301% and 400% relative to control +++
+ +++ at 401% over control
Table 1: compounds prepared by the process of the invention
| Examples of the invention | Chemical name | Activity of |
| 1 | N- (2- (4- (dimethylamino) phenyl) benzo [ d ]]Oxazol-5-yl) isonicotinamides | + |
| 2 | N- (2- (4-fluorophenyl) benzo [ d)]Oxazol-5-yl) furan-2-carboxamide | + |
| 3 | 2- ((4-chlorophenoxy) methyl) -1-methyl-1H-benzo [ d]Imidazole | +++ |
| 4 | 2- ((4-methoxyphenoxy) methyl) -1H-benzo [ d]Imidazole | ++ |
| 5 | Phenyl (2-phenyl-1H-benzo [ d ]]Imidazol-6-yl) methanones | + |
| 6 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) nicotinamide | + |
| 7 | 3-phenyl-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) propanamides | + |
| 8 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) acetamide | ++ |
| 9 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) propanamides | ++ |
| 10 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) butanamide | +++ |
| 11 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) pentanamide | ++ |
| 12 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) isobutyramide | ++ |
| 13 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) furan-2-carboxamide | ++ |
| 14 | 2-phenylbenzo [ d ]]Oxazol-5-amines | +++ |
| 15 | 2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-amines | + |
| 16 | 2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-amines | ++ |
| 17 | 2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-amines | + |
| 18 | 2-p-tolylbenzo [ d]Oxazol-5-amines | + |
| 19 | 4-chloro-N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 20 | 4-methoxy-N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 21 | 2- (5-Nitro)Radical benzo [ d ]]Oxazol-2-yl) phenol | + |
| 22 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) isonicotinamides | + |
| 23 | 4-chloro-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 24 | 4-methyl-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 25 | 4-methoxy-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 26 | 2-methoxy-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 27 | 4- (dimethylamino) -N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 28 | 3, 4-dichloro-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 29 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) -4- (trifluoromethyl) benzamide | + |
| 30 | 3, 5-dichloro-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 31 | 4-fluoro-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | + |
| 32 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) biphenyl-4-carboxamides | + |
| 33 | 2-phenyl-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) acetamide | + |
| 34 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) cinnamamides | + |
| 35 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) -1-naphthamides | + |
| 36 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) -2-naphthamides | + |
| 37 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) thiophene-2-carboxamides | ++ |
| 38 | 2- (5-aminobenzo [ d ]]Oxazol-2-yl) phenol | +++ |
| 39 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 40 | 4-chloro-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 41 | 4-methyl-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 42 | 4-methoxy-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 43 | 2-methoxy-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 44 | 4- (dimethylamino) -N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 45 | 3, 4-dichloro-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 46 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) -4- (trifluoromethyl) benzamide | + |
| 47 | 3, 5-dichloro-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 48 | 4-fluoro-N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 49 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) biphenyl-4-carboxamides | + |
| 50 | 2-phenyl-N- (2- (pyrid-3-yl) benzo [ d]Oxazol-5-yl) acetamide | + |
| 51 | 3-phenyl-N- (2- (pyrid-3-yl) benzo [ d]Oxazol-5-yl) propanamides | + |
| 52 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) cinnamamides | + |
| 53 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) propanamides | + |
| 54 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) butanamide | + |
| 55 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) pentanamide | + |
| 56 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) isobutyramide | ++ |
| 57 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) furan-2-carboxamide | + |
| 58 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) furan-2-carboxamide | + |
| 59 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzamides | ++ |
| 60 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) nicotinamide | ++ |
| 61 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) isonicotinamides | + |
| 62 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 63 | 4-chloro-N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 64 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -4-methylbenzamide | + |
| 65 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -4-methoxybenzamide | + |
| 66 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -2-methoxybenzamide | + |
| 67 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -4- (dimethylamino) benzamide | ++ |
| 68 | 3, 4-dichloro-N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 69 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -4- (trifluoromethyl) benzamide | + |
| 70 | 3, 5-dichloro-N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 71 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -4-fluorobenzamides | + |
| 72 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) biphenyl-4-carboxamides | + |
| 73 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -2-phenylacetamides | ++ |
| 74 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) -3-phenylpropionamides | + |
| 75 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) propanamides | ++ |
| 76 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) butanamide | + |
| 77 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) pentanamide | ++ |
| 78 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 79 | N- (2- (4- (diethylamino) phenyl) benzo [ d]Oxazol-5-yl) thiophene-2-carboxamides | + |
| 80 | 3- (5-Propylbenzo [ d ]]Oxazol-2-yl) benzoic acid | + |
| 81 | N- (2- (pyridin-3-yl) benzo [ d]Oxazol-5-yl) nicotinamide | + |
| 82 | 5-amino-2- (5-aminobenzo [ d ]]Oxazol-2-yl) phenol | ++ |
| 83 | 4-methoxy-N- (2- (4-methyl)Oxyphenyl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 84 | 5- (ethylsulfonyl) -2-phenylbenzo [ d]Oxazole (oxazole) | ++ |
| 85 | 2, 5-biphenylbenzo [ d ]]Oxazole (oxazole) | +++ |
| 86 | 2-phenylnaphthalene [1, 2-d ]]Oxazole (oxazole) | +++ |
| 87 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) isonicotinamides | + |
| 88 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) benzamides | + |
| 89 | 4-chloro-N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) benzamides | + |
| 90 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -4-methylbenzamide | + |
| 91 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -4-methoxybenzamide | + |
| 92 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -2-methoxybenzamide | + |
| 93 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -4- (dimethylamino) benzamide | + |
| 94 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -4- (trifluoromethyl) benzamide | + |
| 95 | 3, 5-dichloro-N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) benzamides | + |
| 96 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -4-fluorobenzamides | + |
| 97 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -2-phenylacetamides | ++ |
| 98 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -3-phenylpropionamides | + |
| 99 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) butanamide | ++++ |
| 100 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) pentanamide | ++ |
| 101 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 102 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) furan-2-carboxamide | + |
| 103 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) thiophene-2-carboxamides | + |
| 104 | 5-amino-2- (5, 6-dimethyl-1H-benzo [ d ]]Imidazol-2-yl) phenol | ++ |
| 105 | 2- (3-methyl-4-nitrophenyl) -1H-benzo [ d]Imidazole | ++++ |
| 106 | 2- (6-nitro-1H-benzo [ d ]]Imidazol-2-yl) phenol | + |
| 107 | 2-phenylbenzo [ d ]]Oxazole-5-carboxylic acid | +++ |
| 108 | 2- (4-Propylphenyl) benzo [ d]Oxazole-5-carboxylic acid | + |
| 109 | 2- (4-Propylphenyl) benzo [ d]Oxazole-6-carboxylic acid | + |
| 110 | 2 '- (4-Propylphenyl) -2, 6' -bibenzo [ d]Oxazole (oxazole)-6-carboxylic acid | + |
| 111 | 5-chloro-2-phenylbenzo [ d ]]Oxazole (oxazole) | ++ |
| 112 | 6-chloro-2-phenylbenzo [ d ]]Oxazole (oxazole) | + |
| 113 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) nicotinamide | + |
| 114 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) isonicotinamides | + |
| 115 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) propanamides | ++++ |
| 116 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) butanamide | ++++ |
| 117 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) pentanamide | +++ |
| 118 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) isobutyramide | ++ |
| 119 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) furan-2-carboxamide | + |
| 120 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) thiophene-2-carboxamides | ++ |
| 121 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) nicotinamide | + |
| 122 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazole ion-treated5-yl) isonicotinamides | + |
| 123 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) acetamide | ++ |
| 124 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) propanamides | + |
| 125 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) butanamide | + |
| 126 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) pentanamide | + |
| 127 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 128 | N- (2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) furan-2-carboxamide | + |
| 129 | 5-tert-butyl-2-phenylbenzo [ d]Oxazole (oxazole) | ++++ |
| 130 | 6-nitro-2-phenylbenzo [ d ]]Oxazole (oxazole) | ++ |
| 131 | 4- (5-chlorobenzo [ d ]]Oxazol-2-yl) -N, N-diethylaniline | +++ |
| 132 | 4- (6-chlorobenzo [ d ]]Oxazol-2-yl) -N, N-diethylaniline | ++++ |
| 133 | 2- (5-amino-1H-benzo [ d ]]Imidazol-2-yl) phenol | + |
| 134 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) isonicotinamides | + |
| 135 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) acetamide | +++ |
| 136 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) propanamides | +++ |
| 137 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) butanamide | ++ |
| 138 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) pentanamide | + |
| 139 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++ |
| 140 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) furan-2-carboxamide | + |
| 141 | N- (2- (4-methoxyphenyl) benzo [ d ]]Oxazol-5-yl) thiophene-2-carboxamides | + |
| 142 | 4- (5-tert-butylbenzo [ d ]]Oxazol-2-yl) -N, N-diethylaniline | ++ |
| 143 | 4- (benzo [ d ]]Oxazol-2-yl) -N, N-diethylaniline | ++ |
| 144 | N, N-diethyl-4- (5- (ethylsulfonyl) benzo [ d ]]Oxazol-2-yl) anilines | + |
| 145 | N, N-diethyl-4- (5-phenylbenzo [ d ]]Oxazol-2-yl) anilines | + |
| 146 | N, N-diethyl-4- (naphtho [1, 2-d ]]Oxazol-2-yl) anilines | ++ |
| 147 | 2- (pyridin-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 148 | N- (2- (4-chlorophenyl) -2H-benzo [ d ]][1，2，3]Triazol-5-yl) propionamide | ++++ |
| 149 | 2- (4- (pyrrolidin-1-yl) phenyl) benzo [ d]Oxazol-5-amines | ++ |
| 150 | 2- (4- (piperidin-1-yl) phenyl) benzo [ d]Oxazol-5-amines | ++ |
| 151 | 2- (4- (4-methylpiperazin-1-yl) phenyl) benzo [ d]Oxazol-5-amines | ++ |
| 152 | 2- (4- (diethylamino) phenyl) benzo [ d]Oxazole-5-carboxylic acid | + |
| 153 | 6-nitro-2-phenyl-oxazolo [5, 4-b]Pyridine compound | + |
| 154 | 2-propylbenzene [ d ]]Oxazol-5-amines | + |
| 155 | 2-phenylbenzo [ d ]]Oxazolyl-6-amines | +++ |
| 156 | N-benzyl-2-phenylbenzo [ d ]]Oxazol-5-amines | +++ |
| 157 | 2-p-tolyloxazolo [5, 4-b ]]Pyridine compound | +++ |
| 158 | 2-p-tolyloxazolo [4, 5-b ]]Pyridine compound | + |
| 159 | 2- (4-Morpholphenyl) benzo [ d]Oxazol-5-amines | + |
| 160 | 3-methoxy-N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) propanamides | ++++ |
| 161 | 5-phenyl-2-p-tolylbenzeneAnd [ d ]]Oxazole (oxazole) | +++ |
| 162 | 2- (4-chlorophenyl) -5-phenylbenzo [ d]Oxazole (oxazole) | + |
| 163 | 2-cyclohexyl-5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 164 | 2- (4-chlorophenyl) -6-nitro-1H-benzo [ d]Imidazole | ++ |
| 165 | N- (2-Benzylbenzo [ d ]]Oxazol-5-yl) -2-phenylacetamides | + |
| 166 | N- (2-p-tolyl-1H-benzo [ d ]]Imidazoyl-5-yl) butanamide | + |
| 167 | N-butyl-2-phenylbenzo [ d ]]Oxazol-5-amines | ++++ |
| 168 | N-isobutyl-2-phenylbenzo [ d ]]Oxazol-5-amines | ++++ |
| 169 | 2-phenyl-oxazolo [5, 4-b ]]Pyridyl-6-amines | + |
| 170 | N- (2-phenyl-oxazolo [5, 4-b ]]Pyridyl-6-yl) butanamides | + |
| 171 | 5-Nitro-2- (pyridin-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 172 | 5-tert-butyl-2-p-tolylbenzo [ d]Oxazole (oxazole) | ++++ |
| 173 | 2-p-tolylbenzo [ d]Oxazole (oxazole) | +++ |
| 174 | 2- (3- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-amines | + |
| 175 | N- (2-p-tolyl-1H-benzo [ d ]]Imidazolyl-5-yl) isobutyramides | + |
| 176 | N-butyl-2-p-tolylbenzo [ d]Oxazole-5-carboxamides | ++ |
| 177 | N-propyl-2-p-tolylbenzo [ d]Oxazole-5-carboxamides | ++++ |
| 178 | N- (2- (4-chlorophenyl) -1H-benzo [ d ]]Imidazoyl-5-yl) butanamide | + |
| 179 | 5- (ethylsulfonyl) -2-p-tolylbenzo [ d]Oxazole (oxazole) | ++++ |
| 180 | 2- (4-chlorophenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 181 | N-isopropyl-2-p-tolylbenzo [ d]Oxazole-5-carboxamides | +++ |
| 182 | N-butyl-2- (4-chlorophenyl) benzo [ d]Oxazol-5-amines | +++ |
| 183 | 2- (4-chlorophenyl) -N-isobutylbenzo [ d ]]Oxazol-5-amines | +++ |
| 184 | N-benzyl-2- (4-chlorophenyl) benzo [ d]Oxazol-5-amines | + |
| 185 | N-butyl-2-p-tolylbenzo [ d]Oxazol-5-amines | +++ |
| 186 | N-isobutyl-2-p-tolylbenzo [ d]Oxazol-5-amines | +++ |
| 187 | N-benzyl-2-p-tolylbenzo [ d]Oxazol-5-amines | +++ |
| 188 | N- (2-phenyl-1H-benzo [ d ]]Imidazolyl-5-yl) isobutyramides | +++ |
| 189 | 4-Nitro-2-p-tolyl radicalBenzo [ d ] carbonyl]Oxazole (oxazole) | + |
| 190 | 6-nitro-2-p-tolylbenzo [ d]Oxazole (oxazole) | +++ |
| 191 | 2- (4-chlorophenyl) -6-nitrobenzo [ d]Oxazole (oxazole) | ++ |
| 192 | 2-p-tolyloxazolo [4, 5-c]Pyridine compound | + |
| 193 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) propane-1-sulfonamides | ++ |
| 194 | N- (2-phenyl-1H-benzo [ d ]]Imidazoyl-5-yl) butanamide | ++ |
| 195 | N- (2- (4-chlorophenyl) -1H-benzo [ d ]]Imidazolyl-5-yl) isobutyramides | ++ |
| 196 | 2-m-tolylbenzo [ d]Oxazol-5-amines | + |
| 197 | 2- (3- (dimethylamino) phenyl) benzo [ d]Oxazol-5-amines | + |
| 198 | 5-bromo-2-p-tolylbenzo [ d]Oxazole (oxazole) | +++ |
| 199 | 5- (4-methoxyphenyl) -2-p-tolylbenzo [ d]Oxazole (oxazole) | + |
| 200 | N- (2-m-tolylbenzo [ d ]]Oxazol-5-yl) butanamide | ++++ |
| 201 | N- (2- (3- (dimethylamino) phenyl) benzo [ d ]]Oxazol-5-yl) butanamide | + |
| 202 | N- (2-m-tolylbenzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 203 | N- (2- (3- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 204 | N- (2- (3- (dimethylamino) phenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 205 | 2-o-tolylbenzo [ d]Oxazol-5-amines | +++ |
| 206 | 2- (2-chlorophenyl) benzo [ d]Oxazol-5-amines | ++ |
| 207 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) propanamides | ++++ |
| 208 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) palmitamides | ++ |
| 209 | 2, 2, 2-trifluoro-N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) acetamide | ++ |
| 210 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) palmitamides | ++ |
| 211 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -2, 2, 2-trifluoroacetamide | ++ |
| 212 | 6-bromo-2-p-tolyloxazolo [5, 4-b ]]Pyridine compound | ++ |
| 213 | 2-p-tolylbenzo [ d]Thiazol-5-amines | + |
| 214 | 2-benzyl-5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 215 | 5, 6-dimethyl-2-P-tolyl benzo [ d ]]Oxazole (oxazole) | ++++ |
| 216 | N- (2-p-tolylbenzo [ d ]]Thiazol-5-yl) butanamide | ++++ |
| 217 | N- (2-p-tolylbenzo [ d ]]Thiazol-5-yl) isobutyramide | ++++ |
| 218 | 2-p-tolylbenzo [ d]Oxazole-5-carboxamides | ++++ |
| 219 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -N-methylpropanamide | +++ |
| 220 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) propane-2-sulfonamides | ++ |
| 221 | N- (2-phenylbenzo [ d ]]Oxazol-5-yl) benzenesulfonamides | + |
| 222 | 2- (4-chlorophenyl) -5, 6-dimethylbenzo [ d ]]Oxazole (oxazole) | ++++ |
| 223 | 6-Nitro-2- (pyridin-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 224 | 2- (2, 4-dichlorophenyl) -5, 6-dimethylbenzo [ d]Oxazole (oxazole) | ++++ |
| 225 | N- (2- (3- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) butanamide | + |
| 226 | N- (2-o-tolylbenzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 227 | N- (2-Benzylbenzo [ d ]]Oxazol-5-yl) butanamide | + |
| 228 | N- (2-Benzylbenzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 229 | N- (2- (2-chlorophenyl) benzo [ d ]]Oxazol-5-yl) butanamide | +++ |
| 230 | N- (2- (2-chlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 231 | N- (2- (3-chlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 232 | 2- (3-fluorophenyl) benzo [ d]Oxazol-5-amines | ++++ |
| 233 | 4, 4, 4-trifluoro-N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) butanamide | + |
| 234 | 2-p-tolylbenzo [ d]Oxazolyl-4-amines | +++ |
| 235 | N- (2-p-tolylbenzo [ d ]]Oxazolyl-4-yl) butanamides | + |
| 236 | N- (2-p-tolylbenzo [ d ]]Oxazolyl-4-yl) isobutyramide | + |
| 237 | 2-p-tolylbenzo [ d]Oxazolyl-6-amines | ++++ |
| 238 | 2- (2, 4-difluorobenzamide) -4, 5-dimethylphenyl 2, 4-difluorobenzoate | + |
| 239 | N- (2- (3-chlorophenyl) benzo [ d ]]Oxazol-5-yl) butanamide | + |
| 240 | 1-phenyl-3- (2-phenylbenzo [ d ]]Oxazol-5-yl) urea | +++ |
| 241 | 1-isopropyl-3- (2-phenylbenzo [ d ]]Oxazol-5-yl) urea | + |
| 242 | N- (2- (2-fluorophenyl) benzo [ d)]Oxazol-5-yl) butanamide | + |
| 243 | N- (2- (2-fluorophenyl) benzo [ d)]Oxazol-5-yl) isobutyramide | +++ |
| 244 | N- (2- (3-fluorophenyl) benzo [ d)]Oxazol-5-yl) butanamide | ++++ |
| 245 | N- (2- (3-fluorophenyl) benzo [ d)]Oxazol-5-yl) isobutyramide | +++ |
| 246 | 3-oxo-3- (2-phenylbenzo [ d ]]Oxazol-5-ylamino) propylcarbamic acid tert-butyl ester | + |
| 247 | 2- (2, 4-difluorophenyl) -5, 6-dimethylbenzo [ d]Oxazole (oxazole) | ++ |
| 248 | N- (2-Cyclohexylbenzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 249 | N- (2-Cyclohexylbenzo [ d ]]Oxazol-5-yl) butanamide | + |
| 250 | 2- (5-butylpyridin-2-yl) -5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 251 | 2-phenylbenzo [ d ]]Thiazol-5-amines | +++ |
| 252 | N- (4- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) phenyl) acetamide | +++ |
| 253 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) propane-1-sulfonamides | + |
| 254 | 3, 3, 3-IIIfluoro-N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) propanamides | ++ |
| 255 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-6-yl) isobutyramide | ++++ |
| 256 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-6-yl) butanamide | ++ |
| 257 | N- (2- (2, 4-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 258 | N- (2- (4-fluorophenyl) benzo [ d)]Oxazol-5-yl) isobutyramide | +++ |
| 259 | N- (2-p-tolylbenzo [ d ]]Oxazol-5-yl) propane-2-sulfonamides | + |
| 260 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) propane-1-sulfonamides | + |
| 261 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) propane-2-sulfonamides | + |
| 262 | 2- (5-butylpyridin-2-yl) -6-nitrobenzo [ d]Oxazole (oxazole) | ++ |
| 263 | 2- (4-chlorophenyl) -N-isopropylbenzo [ d ]]Oxazole-5-carboxamides | +++ |
| 264 | 2- (4-chlorophenyl) benzo [ d]Oxazole-5-carboxamides | ++++ |
| 265 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) cyclopropanecarboxamides | ++++ |
| 266 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) cyclobutanecarboxamide | +++ |
| 267 | N- (2-phenylbenzo [ d ]]Thiazol-5-yl) isobutyramide | ++++ |
| 268 | N- (2- (3, 4-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 269 | 2- (4-chlorophenyl) -5- (4- (ethylsulfonyl) phenyl) benzo [ d]Oxazole (oxazole) | + |
| 270 | N- (2- (5-chloropyridin-2-yl) benzo [ d]Oxazol-5-yl) isobutyramide | ++++ |
| 271 | N- (2- (3, 5-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++ |
| 272 | (S) -2-amino-N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) propanamides | +++ |
| 273 | N- (2- (2, 3-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | ++++ |
| 274 | 2- (4-chlorophenyl) -N-isopropylbenzo [ d ]]Oxazole-5-thiocarboxamides | + |
| 275 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -2-methylpropanethioamides | ++ |
| 276 | 2- (4-chlorophenyl) benzo [ d]Thiazol-5-amines | ++++ |
| 277 | N- (2- (4-chlorophenyl) benzo [ d ]]Thiazol-5-yl) isobutyramide | +++ |
| 278 | 2- (4-chlorophenyl) -N-isopropyl-N-methylbenzo [ d]Oxazole-5-carboxamides | +++ |
| 279 | 2- (4-chlorophenyl) -N-methylbenzo [ d ]]Oxazole-5-carboxamides | +++ |
| 280 | 2-Phenethylbenzo [ d ]]Oxazol-5-amines | ++++ |
| 281 | 2- (4-chlorophenyl) -5- (isopropylsulfone) benzo [ d]Oxazole (oxazole) | ++++ |
| 282 | 2- (2-chlorophenyl) benzo [ d]Thiazol-5-amines | ++++ |
| 283 | 2- (3-chlorophenyl) benzo [ d]Thiazol-5-amines | ++++ |
| 284 | 2- (3, 4-dichlorophenyl) benzo [ d]Thiazol-5-amines | ++++ |
| 285 | 3-morpholino-N- (2-phenylbenzo [ d ]]Oxazol-5-yl) propanamides | + |
| 286 | 2- (benzo [ d ]][1，3]Dioxolen-5-yl) -5-nitrobenzo [ d]Oxazole (oxazole) | +++ |
| 287 | 4- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) benzoic acid methyl ester | + |
| 288 | 5-bromo-2- (4-chlorophenyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 289 | 4- (5-chlorobenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 290 | 4- (6-chlorobenzo [ d ]]Oxazol-2-yl) anilines | +++ |
| 291 | 2- (4-chlorophenyl) -5- (4-morpholinophenyl) benzo [ d]Oxazole (oxazole) | ++ |
| 292 | 2- (4-chlorophenyl) -5- (3- (ethylthio) phenyl) benzo [ d]Oxazole (oxazole) | ++ |
| 293 | 2- (3-chlorophenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 294 | N- (2- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) phenyl) acetamide | + |
| 295 | N- (2- (2-chlorophenyl) benzo [ d ]]Thiazol-5-yl) isobutyramide | ++++ |
| 296 | N- (2- (3-chlorophenyl) benzo [ d ]]Thiazol-5-yl) isobutyramide | ++++ |
| 297 | N- (2- (3, 4-dichlorophenyl) benzo [ d ]]Thiazol-5-yl) isobutyramide | ++++ |
| 298 | 2- (2-chlorophenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++ |
| 299 | 2- (benzo [ d ]][1，3]Dioxolen-5-yl) benzo [ d]Oxazol-5-amines | ++ |
| 300 | N- (2- (benzo [ d ])][1，3]Dioxolen-5-yl) benzo [ d]Oxazol-5-yl) isobutyramide | +++ |
| 301 | 2- (3, 4-dichlorophenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++ |
| 302 | N- (2-Phenylethylbenzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 303 | N- (2- (2, 3-dichlorophenyl) benzo [ d ]]Thiazol-5-yl) isobutyramide | +++ |
| 304 | 2- (2, 3-dichlorophenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 305 | 2- (4-chlorophenyl) -5- (6-methoxypyridin-3-yl) benzo [ d]Oxazole (oxazole) | ++ |
| 306 | 2- (4-chlorophenyl) -5- (6-methoxypyridin-3-yl) benzo [ d]Oxazole (oxazole) | + |
| 307 | 2- (2, 3-dichlorophenyl) benzo [ d]Thiazol-5-amines | +++ |
| 308 | 2- (1-phenylethyl) benzo [ d]Oxazol-5-amines | + |
| 309 | N- (2- (1-phenylethyl) benzo [ d)]Oxazol-5-yl) isobutyramide | + |
| 310 | 2- (4-chlorophenyl) -5, 6-methylenedioxybenzoxazole | +++ |
| 311 | N- (2- (2, 5-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 312 | 2- (4-chlorophenyl) benzo [ d]Oxazole-5-sulfonic acid | + |
| 313 | 3- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) benzoic acid | + |
| 314 | 2- (4-chlorophenyl) -5- (6-chloropyridin-3-yl) benzo [ d]Oxazole (oxazole) | + |
| 315 | 2- (4-chlorophenyl) -5- (6-fluoropyridin-3-yl) benzo [ d]Oxazole (oxazole) | + |
| 316 | 2- (4-chlorophenyl) -5- (6-morpholinopyridin-3-yl) benzo [ d]Oxazole (oxazole) | + |
| 317 | N- (4- (5-chlorobenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | +++ |
| 318 | N- (4- (5-chlorobenzo [ d ]]Oxazol-2-yl) phenyl) isobutyramide | ++ |
| 319 | N- (4- (5-chlorobenzo [ d ]]Oxazol-2-yl) phenyl) thiophene-2-carboxamides | + |
| 320 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -N-methylisobutylamide | ++ |
| 321 | 5-tert-butyl-2- (4-chlorophenyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 322 | 2- (4-chlorophenyl) -N-isobutyl-N-methylbenzo [ d]Oxazol-5-amines | + |
| 323 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -3-methoxypropionamides | ++++ |
| 324 | 2- (3, 4-dichlorophenyl) -6-nitrobenzo [ d]Oxazole (oxazole) | ++ |
| 325 | 2- (4-chlorophenyl) benzo [ d]Oxazole-5-sulfonamides | ++++ |
| 326 | 5-chloro-2- (4-chlorophenyl) -6-nitrobenzo [ d]Oxazole (oxazole) | +++ |
| 327 | 2- (4-chlorophenyl) -5- (6-methoxypyridin-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 328 | 3- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) anilines | ++++ |
| 329 | 4- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) anilines | ++++ |
| 330 | 5-chloro-2- (pyridin-4-yl) benzo [ d]Oxazole (oxazole) | + |
| 331 | 6-chloro-2- (pyridine-4-yl) benzo [ d]Oxazole (oxazole) | + |
| 332 | N- (4- (6-chlorobenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | +++ |
| 333 | N- (4- (6-chlorobenzo [ d ]]Oxazol-2-yl) phenyl) isobutyramide | ++ |
| 334 | N- (4- (6-chlorobenzo [ d ]]Oxazol-2-yl) phenyl) thiophene-2-carboxamides | + |
| 335 | 2- (4-chlorophenyl) -N, N-diisobutylbenzo [ d ]]Oxazol-5-amines | + |
| 336 | 4- (5-bromobenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 337 | 4-amino-N- (4- (5-bromobenzo [ d ]]Oxazol-2-yl) phenyl) benzamides | + |
| 338 | 5- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) pyridyl-2-amines | ++++ |
| 339 | 2- (4-chlorophenyl) -5-phenyl-1H-indole | + |
| 340 | N- (2- (2-chloro-4-fluorophenyl) benzo [ d]Oxazol-5-yl) isobutyramide | ++++ |
| 341 | N- (2- (2-chloro-6-fluorophenyl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 342 | N- (2- (3-chloro-2-fluorophenyl) benzo [ d]Oxazol-5-yl) isobutyramide | ++++ |
| 343 | N- (2- (4-chloro-2-fluorophenyl) benzo [ d]Oxazol-5-yl) isobutyramide | ++++ |
| 344 | N- (2- (2-chloro-5-fluorophenyl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 345 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -3, 3, 3-trifluoropropionamide | +++ |
| 346 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) cyclopentanecarboxamide | + |
| 347 | N- (5-chloro-2- (4-chlorophenyl) benzo [ d ]]Oxazol-6-yl) isobutyramide | ++ |
| 348 | 5-Nitro-2- (4- (trifluoromethoxy) phenyl) benzo [ d]Oxazole (oxazole) | ++ |
| 349 | N- (2- (tetrahydro-2H-pyran-4-yl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 350 | 2- (4- (trifluoromethoxy) phenyl) benzo [ d]Oxazol-5-amines | ++ |
| 351 | N- (2- (3, 4-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) cyclopropanecarboxamides | ++++ |
| 352 | N- (2- (3, 4-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) -3, 3, 3-trifluoropropionamide | ++++ |
| 353 | N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-6-yl) cyclopropanecarboxamides | ++ |
| 354 | N- (2- (2, 3-dichlorophenyl) benzo [ d ]]Oxazol-6-yl) isobutyramide | +++ |
| 355 | N- (2- (4- (trifluoromethoxy) phenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 356 | 4- (5- (4-chlorophenyl) benzo [ d ]]Oxazol-2-yl) anilines | + |
| 357 | 2-morpholino-5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 358 | N- (5- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) pyridin-2-yl) acetamide | + |
| 359 | N- (4- (5-bromobenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | ++++ |
| 360 | 2-morpholinobenzo [ d ]]Oxazol-5-amines | + |
| 361 | 2- (3, 4-chlorophenyl) -5, 6-methylenedioxybenzoxazole | + |
| 362 | (S) -N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) pyrrolidine-2-carboxamides | ++ |
| 363 | N- (2- (2, 3-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) -3, 3, 3-trifluoropropionamide | ++++ |
| 364 | N- (2-cyclopentylbenzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 365 | N- (4- (5-acetamidobenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | + |
| 366 | 2- (furan-2-yl) -5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 367 | N- (4- (2- (4-chlorophenyl) -1H-indol-5-yl) phenyl) acetamide | + |
| 368 | N- (2- (2-chloro-3- (trifluoromethyl) phenyl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 369 | 2- (3, 4-dichlorophenyl) benzo [ d]Oxazolyl-6-amines | ++++ |
| 370 | N- (2- (3, 4-dichlorophenyl) benzo [ d ]]Oxazol-6-yl) isobutyramide | ++++ |
| 371 | 2- (benzo [ d ]][1，3]Dioxolen-5-yl) -5-chloro-6-nitrobenzo [ d]Oxazole (oxazole) | +++ |
| 372 | N- (4- (5- (4-chlorophenyl) benzo [ d ]]Oxazol-2-yl) phenyl) acetamide | + |
| 373 | N- (2- (naphthalen-2-yl) benzo [ d]Oxazol-5-yl) acetamide | ++++ |
| 374 | N- (2- (4-acetamidophenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 375 | N- (2-phenyl-1H-indol-6-yl) isobutyramide | + |
| 376 | 2, 3-dichloro-N- (2- (2, 3-dichlorophenyl) benzo [ d]Oxazol-5-yl) benzamides | + |
| 377 | (S) -N- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) -2- (methylamino) propanamide | +++ |
| 378 | N- (1-methyl-1H-indol-6-yl) isobutyramide | + |
| 379 | 2- (4-Chlorophenylthio) -5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 380 | 2- (4-Chlorobenzoylmethylthio) benzo [ d]Oxazol-5-amines | + |
| 381 | N2- (4-chlorophenylmethyl) benzo [ d]Oxazole-2, 5-diamines | + |
| 382 | 2- (4-Methylbenzylthio) -5-nitro compoundRadical benzo [ d ]]Oxazole (oxazole) | + |
| 383 | N- (2- (4-chlorophenylmethylthio) benzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 384 | N- (2- (naphthalen-2-yl) benzo [ d]Oxazol-5-yl) isobutyramide | +++ |
| 385 | N- (2- (naphthalen-2-yl) benzo [ d]Oxazol-5-yl) thiophene-2-carboxamides | + |
| 386 | 2- (4-chlorophenyl) benzo [ d]Oxazol-5-yl-carbamic acid ethyl ester | + |
| 387 | N- (1-benzyl-1H-indol-6-yl) isobutyramide | + |
| 388 | 5-Nitro-2- (thien-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 389 | N- (1-methyl-2-phenyl-1H-indol-6-yl) isobutyramide | + |
| 390 | 5- (ethylsulfonyl) -2- (naphthalen-2-yl) benzo [ d]Oxazole (oxazole) | +++ |
| 391 | 2- (3-chloro-2-fluorophenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++ |
| 392 | 2-cyclohexyl-5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 393 | 2- (5-Chloropyridin-2-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++ |
| 394 | 2- (benzene)And [ d ]][1，3]Dioxolen-5-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 395 | 5-chloro-2- (4- (methylsulfonyl) phenyl) benzo [ d]Oxazole (oxazole) | ++ |
| 396 | N- (2-phenylbenzofuran-5-yl) isobutyramide | ++++ |
| 397 | 2- (benzo [ d ]][1，3]Dioxolen-5-yl) -5-chlorobenzo [ d]Oxazolyl-6-amines | +++ |
| 398 | N- (2- (benzo [ d ])][1，3]Dioxolen-5-yl) -5-chlorobenzo [ d]Oxazol-6-yl) isobutyramide | + |
| 399 | 2- (4-chlorophenyl) -6- (methylthio) benzo [ d]Thiazoles | +++ |
| 400 | 2- (4-chlorophenyl) -5- (methylsulfonyl) benzo [ d]Oxazole (oxazole) | ++ |
| 401 | 2- (Biphenyl-4-yl) benzo [ d]Oxazol-5-amines | +++ |
| 402 | 2- (Quinolin-2-yl) benzo [ d]Oxazol-5-amines | +++ |
| 403 | 2- (quinolin-3-yl) benzo [ d]Oxazol-5-amines | +++ |
| 404 | 2- (6-Methoxynaphthalen-2-yl) benzo [ d]Oxazol-5-amines | ++ |
| 405 | 2- (6-Bromomaphthalen-2-yl) benzo [ d]Oxazol-5-amines | + |
| 406 | 2- (4-chlorophenyl) -6- (methylsulfonyl) benzo [ d]Thiazoles | ++++ |
| 407 | S-2- (4-chlorophenyl) benzo [ d]Oxazol-5-yl ethyl thiol ester | + |
| 408 | 2-phenyl-5- (3 ', 3 ', 3 ' -trifluoropropionamide) benzofuran | + |
| 409 | 2- (4-chlorophenyl) naphtho [1, 2-d]Oxazole (oxazole) | ++++ |
| 410 | N- (2- (naphthalen-1-yl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 411 | N- (2- (biphenyl-4-yl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 412 | N- (2- (6-methoxynaphthalen-2-yl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 413 | N- (2- (6-bromonaphthalen-2-yl) benzo [ d]Oxazol-5-yl) isobutyramide | + |
| 414 | 2- (4' -chlorophenyl) -5-isobutyramide-benzofuran | + |
| 415 | N- (2- (quinolin-3-yl) benzo [ d]Oxazol-5-yl) isobutyramide | ++++ |
| 416 | N- (2- (quinolin-2-yl) benzo [ d]Oxazol-5-yl) isobutyramide | ++++ |
| 417 | 1- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) propan-1-one | ++++ |
| 418 | 5- (ethylsulfonyl) -2- (5-methylthiophen-2-yl) benzo [ d]Oxazole (oxazole) | ++++ |
| 419 | N- (2- (furan-2-yl) benzo [ d)]Oxazol-5-yl) isobutyramide | ++++ |
| 420 | 1- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) ethaneones | ++++ |
| 421 | 2- (4-cyclohexylphenyl) benzo [ d]Oxazol-5-amines | ++++ |
| 422 | 5- (ethylsulfonyl) -2- (quinolin-2-yl) benzo [ d]Oxazole (oxazole) | ++++ |
| 423 | 5- (ethylsulfonyl) -2- (quinolin-3-yl) benzo [ d]Oxazole (oxazole) | ++++ |
| 424 | 2- (6-Bromomaphthalen-2-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 425 | 2- (4-Cyclohexylphenyl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 426 | 2- (Biphenyl-4-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 427 | 5- (ethylsulfonyl) -2- (naphthalen-1-yl) benzo [ d]Oxazole (oxazole) | + |
| 428 | 5-amino-2- (5, 6-dichlorobenzo [ d ]]Oxazol-2-yl) phenol | +++ |
| 429 | 5- (ethylsulfonyl) -2- (thiophen-2-yl) benzo [ d]Oxazole (oxazole) | ++ |
| 430 | N- (2- (4-cyclohexylphenyl) benzo [ d ]]Oxazol-5-yl) isobutyramide | + |
| 431 | 5- (ethylsulfonyl) -2- (6-fluoronaphthalen-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 432 | 2- (benzo [ b ]]Thien-5-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 433 | N- (4- (5, 6-dimethylbenzo [ d ]]Oxazol-2-yl) -3-hydroxyphenyl) acetamides | ++ |
| 434 | 2- (3, 4-dichlorophenyl) -5- (isopropyl sulfone) benzo [ d]Oxazole (oxazole) | +++ |
| 435 | N- (4- (5, 6-dimethylbenzo [ d ]]Oxazol-2-yl) -3-hydroxyphenyl) acetamides | ++ |
| 436 | 5- (ethylsulfonyl) -2- (3-methylthiophen-2-yl) benzo [ d]Oxazole (oxazole) | ++ |
| 437 | 2- (5- (ethylsulfonyl) benzo [ d ]]Oxazol-2-yl) naphthalen-1-ols | ++++ |
| 438 | 2- (2, 2-difluorobenzo [ d ]][1，3]Dioxolen-5-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 439 | 2- (4' -chlorophenyl) -5- (N, N-diethylsulphonamide) -benzoxazole | + |
| 440 | 4- (5, 6-Dichlorobenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 441 | 5- (ethylsulfonyl) -2- (5-methylfuran-2-yl) benzo [ d]Oxazole (oxazole) | +++ |
| 442 | N- (4- (naphtho [1, 2-d ]]Oxazol-2-yl) phenyl) isobutyramide | +++ |
| 443 | 5- (ethylsulfonyl) -2- (4-methylthiophen-2-yl) benzo [ d]Oxazole (oxazole) | ++++ |
| 444 | 5- (ethylsulfonyl) -2- (5, 6, 7, 8-tetrahydronaphthalen-2-yl) benzo [ d]Oxazole (oxazole) | +++ |
| 445 | 2- (benzofuran-5-yl) -5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 446 | 2- (4 '-chlorophenyl) -5- (1' -hydroxyethyl) -benzoxazole | ++++ |
| 447 | 5-amino-2- (5- (ethylsulfonyl) benzo [ d]Oxazol-2-yl) phenol | ++ |
| 448 | 2- (naphthalen-2-yl) -5- (trifluoromethoxy) benzo [ d]Oxazole (oxazole) | ++++ |
| 449 | 2- (naphthalen-2-yl) benzo [ d]Oxazole-5-carboxylic acid | ++-++ |
| 450 | 2- (naphthalen-2-yl) benzo [ d]Oxazole (oxazole) | ++++ |
| 451 | 5-tert-butyl-2- (naphthalen-2-yl) benzo [ d]Oxazole (oxazole) | + |
| 452 | 5, 6-difluoro-2- (naphthalen-2-yl) benzo [ d]Oxazole (oxazole) | ++++ |
| 453 | 1- (2 ' - (3 ', 4 ' -dichlorophenyl) benzo [ d]Oxazol-5' -yl) ethaneones | ++++ |
| 454 | N- (4- (benzo [ d ])]Oxazol-2-yl) phenyl) isobutyramide | ++++ |
| 455 | 2- (4-chlorophenyl) benzo [ d]Oxazol-5-yl (ethyl) phosphinic acid methyl ester | ++++ |
| 456 | 2- (3 ', 4 ' -dichlorophenyl) -5- (1 ' -hydroxyethyl) -benzoxazole | ++++ |
| 457 | 2- (4-chlorophenyl) -6-methylbenzo [ d ]]Oxazole (oxazole) | ++++ |
| 458 | 5-methyl-2- (naphthalen-2-yl) benzo [ d]Oxazole (oxazole) | ++++ |
Table 2: compounds prepared by analogous methods to those described above or by methods known in the art or disclosed in the literature
| 459 | Chemical name | Activity of |
| 460 | 2- (4- ((4-chlorophenylthio) methyl) phenyl) -1H-benzo [ d]Imidazole | + |
| 461 | 2- ((2, 4-Dichlorophenoxy) methyl) -1H-benzo [ d]Imidazole | +++ |
| 462 | 2, 6-dichloro-N- (5-methylbenzo [ d ]]Thiazol-2-ylcarbamoyl) benzamide | + |
| 463 | 2- (thien-2-yl) -1H-benzo [ d]Imidazole | + |
| 464 | N- (3- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) benzamides | + |
| 465 | 1- (2-chlorophenylmethyl) -2- ((2, 4-dichlorophenoxy) methyl) -1H-benzo [ d]Imidazole | + |
| 466 | 1- (2-methylbenzo [ d ]]Oxazol-6-yl) -3-phenylureas | + |
| 467 | 1-methyl-3- (2-methylbenzo [ d ]]Oxazol-6-yl) urea | + |
| 468 | 2-chloro-N- (2-Methylbenzo [ d ] s]Oxazol-6-ylcarbamoyl) benzamide | + |
| 469 | 2- (4-chlorophenyl) -5- (piperidin-1-ylmethyl) benzo [ d]Oxazole (oxazole) | + |
| 470 | 2- (4-methoxyphenyl) -1H-benzo [ d]Imidazole | ++ |
| 471 | 2- (phenoxymethyl) -1H-benzo [ d]Imidazole | ++ |
| 472 | 1-methyl-2- (4-nitrophenyl) -1H-benzo [ d]Imidazole | + |
| 473 | 2- ((4-methoxyphenoxy) methyl) -1H-benzo [ d]Imidazole | ++ |
| 474 | 1-methyl-2- (phenoxymethyl) -1H-benzo [ d]Imidazole | + |
| 475 | 4- (1H-benzo [ d ]]Imidazol-2-yl) anilines | + |
| 476 | 2, 2' - (1, 4-phenylene) bis (1H-benzo [ d)]Imidazolyl-6-amines | + |
| 477 | 2- (4-Nitrophenyl) benzo [ d]Oxazole (oxazole) | + |
| 478 | 4- (benzo [ d ]]Oxazol-2-yl) anilines | ++ |
| 479 | 5- (benzo [ d ]]Thiazol-2-yl) -2-methylaniline | ++ |
| 480 | 2- (3, 4-dichlorophenyl) benzo [ d]Oxazol-5-amines | ++ |
| 481 | 2- (4-ethylphenyl) benzo [ d]Oxazol-5-amines | ++ |
| 482 | 2- (3, 5-dimethylphenyl) benzo [ d]Oxazol-5-amines | + |
| 483 | 2- (benzo [ d ]]Thiazol-2-yl) phenol | + |
| 484 | 5-amino-2- (benzo [ d ]]Oxazol-2-yl) phenol | ++ |
| 485 | 4- (5, 6-Dimethylbenzo [ d ]]Oxazol-2-yl) anilines | ++ |
| 486 | 4- (benzo [ d ]]Oxazol-2-yl) -N, N-dimethylaniline | + |
| 487 | 2- (4-aminophenyl) -1H-benzo [ d ]]Imidazolyl-6-amines | + |
| 488 | 2- (4-chlorophenyl) benzo [ d]Oxazol-5-amines | ++ |
| 489 | 2- (3-chlorophenyl) benzo [ d]Oxazol-5-amines | ++ |
| 490 | 2- (4-aminophenyl) -1-methyl-1H-benzo [ d]Imidazolyl-5-amines | + |
| 491 | 2- (4- (dimethylamino) phenyl) benzo [ d]Oxazol-5-amines | ++ |
| 492 | 5-nitro-2-phenylbenzo [ d ]]Oxazole (oxazole) | ++ |
| 493 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -2- (thiophen-2-yl) acetamide | + |
| 494 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -3, 4-dimethoxybenzamide | + |
| 495 | 2- ((4-chlorophenoxy) methyl) -1H-benzo [ d]Imidazole | + |
| 496 | 4- (5-aminobenzo [ d ]]Oxazol-2-yl) phenol | ++ |
| 497 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) benzamides | + |
| 498 | 4- (1H-benzo [ d ]]Imidazol-2-yl) -N, N-dimethylaniline | + |
| 499 | 2- (methoxymethyl) -1H-benzo [ d]Imidazole | + |
| 500 | N- (2- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -2, 4-dichlorobenzamide | + |
| 501 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -2-phenylacetamide | + |
| 502 | 3- (5-ethylbenzo [ d ]]Oxazol-2-yl) anilines | ++ |
| 503 | N- (3- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) acetamide | + |
| 504 | N- (3- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) thiophene-2-carboxamide | + |
| 505 | 5-methyl-2- (4-nitrophenyl) benzo [ d]Oxazole (oxazole) | ++ |
| 506 | 4- (6-methylbenzo [ d ]]Oxazol-2-yl) anilines | + |
| 507 | 2- (2-fluorophenyl) -1H-benzo [ d]Imidazole | ++ |
| 508 | 2- (furan-2-yl) -5-nitro-1H-benzo [ d]Imidazole | + |
| 509 | N, N-dimethyl-4- (5-nitro-1H-benzo [ d ]]Imidazol-2-yl) anilines | ++ |
| 510 | 2- (furan-2-yl) -1H-benzo [ d]Imidazolyl-5-amine hydrochloride | + |
| 511 | N- (2- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -4- (pyrrolidin-1-ylsulfonyl) benzamide | + |
| 512 | 2- (4-methoxyphenyl) benzo [ d]Oxazol-5-amines | + |
| 513 | N- (3- (benzo [ d ])]Thiazol-2-yl) phenyl) acetamide | + |
| 514 | 2- (3-chlorophenyl) -1H-benzo [ d]Imidazole | + |
| 515 | 2- (3, 4-Dimethoxyphenyl) benzo [ d]Oxazol-5-amines | ++ |
| 516 | 2- (4- (piperidin-1-ylsulfonylphenyl) benzo [ d]Thiazoles | ++ |
| 517 | N- (2- (2, 4-dichlorophenyl) benzo [ d ]]Oxazol-5-yl) acetamide | ++ |
| 518 | 4- (5, 7-Dichlorobenzo [ d ]]Oxazol-2-yl) anilines | ++ |
| 519 | N- (2- (3-chloro-4-methoxyphenyl) benzo [ d]Oxazol-5-yl) acetamide | ++ |
| 520 | 2- (3, 4-Dimethoxyphenyl) -5-nitro-1H-benzo [ d]Imidazole | + |
| 521 | 2- (3, 4-Dimethoxyphenyl) -1-methyl-1H-benzo [ d]Imidazole | + |
| 522 | 2- (2-methoxyphenyl) benzo [ d]Thiazoles | + |
| 523 | 2- (4-chloro-3-nitrophenyl) benzo [ d]Thiazoles | + |
| 524 | 2- (2-chloro-5-nitrophenyl) benzo [ d]Thiazoles | + |
| 525 | 2- (4-fluorophenyl) -5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 526 | 2- (3-chloro-4-methylphenyl) benzo [ d]Oxazol-5-amines | ++ |
| 527 | 2- (2-chloro-4-methylphenyl) benzo [ d]Oxazol-5-amines | ++ |
| 528 | 2- ((4-Methoxyphenoxy) methyl) -1-methyl-1H-benzo [ d]Imidazole | ++ |
| 529 | N- (4- (5, 7-dimethylbenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | ++ |
| 530 | 2- ((1H-benzo [ d)]Imidazol-2-yl) methylthio) -5-phenyl-1, 3, 4-oxadiazole | + |
| 531 | 2- (p-tolyloxymethyl) -1H-benzo [ d]Imidazole | ++ |
| 532 | 4- (5-methyl-1H-benzo [ d ]]Imidazol-2-yl) anilines | + |
| 533 | 5-nitro-2-m-tolylbenzo [ d]Oxazole (oxazole) | ++ |
| 534 | N- (2- (furan-2-yl) -1H-benzo [ d)]Imidazolyl-5-yl) acetamides | + |
| 535 | 2- (4-methoxyphenyl) -1H-benzo [ d]Imidazolyl-5-amines | ++ |
| 536 | N- (2- (furan-2-yl) -1H-benzo [ d)]Imidazolyl-5-yl) -4-methylbenzenesulfoneAmides of carboxylic acids | + |
| 537 | 2- (3, 4-Dimethoxyphenyl) -5-nitrobenzo [ d]Oxazole (oxazole) | + |
| 538 | N- (3- (6-methyl-1H-benzo [ d ]]Imidazol-2-yl) phenyl) furan-2-carboxamide | + |
| 539 | 5-chloro-2- (3-methyl-4-nitrophenyl) benzo [ d]Oxazole (oxazole) | + |
| 540 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) benzo [ d][1，3]Dioxole-5-carboxylic acid esters | + |
| Amines as pesticides | ||
| 541 | 2- (4-chlorophenyl) -1-methyl-1H-benzo [ d]Imidazole | ++ |
| 542 | N- (5- (benzo [ d ])]Thiazol-2-yl) -2-methoxyphenyl) acetamide | ++ |
| 543 | 2- (4- (methylthio) phenyl) -1H-benzo [ d]Imidazole | ++ |
| 544 | 2- (4-aminophenyl) benzo [ d]Oxazolyl-6-amines | ++ |
| 545 | 2- (4- (6-methylbenzo [ d ]]Thiazol-2-yl) phenylcarbamoyl) benzoic acid | + |
| 546 | (Z) -1- (benzo [ d ]]Thiazol-2-yl) -4- (1- (cyclopropylamino) acetal) -3-methyl-1H-pyrazol-5 (4H) -one | + |
| 547 | (E) -2-styryl-1H-benzo [ d ]]Imidazole | +++ |
| 548 | 2- ((2, 5-dimethylphenoxy) methyl) -1H-benzo [ d]Imidazole | + |
| 549 | 2- (4-Ethoxyphenyl) benzo [ d]Oxazol-5-amines | + |
| 550 | 4-amino-2- (5-aminobenzo [ d ]]Thiazol-2-yl) phenol | + |
| 551 | 4-amino-2- (5-ethylbenzo [ d ]]Oxazol-2-yl) phenol | + |
| 552 | 2- (2-phenylhydrazino) benzo [ d]Thiazoles | + |
| 553 | 4- (5-ethylbenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 554 | 2- (5-methyl-1H-benzo [ d ]]Imidazol-2-yl) anilines | +++ |
| 555 | N- (6-ethoxybenzo [ d ]]Thiazol-2-yl) benzamides | + |
| 556 | N- (4- (6-acetamide-5-chloro-1H-benzo [ d)]Imidazol-2-yl) phenyl) acetamide | + |
| 557 | 4- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenoxy) phenylamines | ++++ |
| 558 | 2- (Biphenyl-4-yl) -1H-benzo [ d]Imidazole | + |
| 559 | 4-amino-2- (5, 6-dimethylbenzo [ d ]]Oxazol-2-yl) phenol | +++ |
| 560 | 2- (4-chlorophenyl) -1H-benzo [ d]Imidazolyl-5-amines | +++ |
| 561 | 2- (thien-2-yl) -1H-naphtho [2, 3-d]Imidazole | +++ |
| 562 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) furan-2-carboxamide | +++ |
| 563 | 2- (Ethio) benzo [ d]Thiazol-6-amines | ++ |
| 564 | N- (4- (6-methylbenzo [ d ]]Oxazol-2-yl) phenyl) isobutyramide | + |
| 565 | 5-amino-2- (5-isopropylbenzo [ d ]]Oxazol-2-yl) phenol | +++ |
| 566 | 3- (5-chlorobenzo [ d ]]Oxazol-2-yl) -2-methylaniline | + |
| 567 | N- (benzo [ d ]]Thiazol-2-yl) -2-chloro-4-methylbenzamide | + |
| 568 | N- (5- (1H-benzo [ d ]]Imidazol-2-yl) -2-methylphenyl) -2, 2, 2-trifluoroacetamide | +++ |
| 569 | 2- (2-fluorophenyl) benzo [ d]Oxazol-5-amines | +++ |
| 570 | 2-butyl-5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 571 | 5- (ethylsulfonyl) -2-propylbenzo [ d ] s]Oxazole (oxazole) | + |
| 572 | 2-Ethyl-5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 573 | 5- (ethylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 574 | 5- (ethylsulfonyl) benzo [ d]Oxazole-2-thiols | + |
| 575 | N- (3- (2- (4-chlorophenyl) benzo [ d ]]Oxazol-5-yl) phenyl) ethaneAmides of carboxylic acids | ++++ |
| 576 | 1- (2-tert-butyl-1H-indol-5-yl) -3-ethylurea | + |
| 577 | 2- (naphthalen-1-yl) benzo [ d]Oxazol-5-amines | + |
| 578 | 2- (4-chlorophenyl) -5- (propylsulfonyl) benzo [ d]Oxazole (oxazole) | + |
| 579 | 2- (4-chlorophenyl) benzo [ d]Oxazolyl-6-ols | ++++ |
| 580 | N- (4- (5-methyl-1H-benzo [ d ]]Imidazol-2-yl) phenyl) furan-2-carboxamide | +++ |
| 581 | Phenyl (2-phenyl-1H-benzo [ d ]]Imidazol-6-yl) methanones | + |
| 582 | 2- (4-methoxyphenyl) benzo [ d]Thiazoles | ++++ |
| 283 | 2- (4-methoxyphenyl) benzo [ d]Oxazole (oxazole) | +++ |
| 584 | 2- (4-methoxyphenyl) -6-nitrobenzo [ d]Oxazole (oxazole) | +++ |
| 585 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) thiophene-2-carboxamide | ++++ |
| 586 | 2- (4-methoxyphenyl) -5-nitro-1H-benzo [ d]Imidazole | ++ |
| 587 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) tetrahydrofuran-2-carboxamide | +++ |
| 588 | 1-methyl-2-p-tolyl-1H-benzo [ d]Imidazole | +++ |
| 589 | N- (4- (benzo [ d ])]Oxazol-2-yl) phenyl) acetamide | +++ |
| 590 | 4- (4, 6-Dimethylbenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 591 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) acetamide | +++ |
| 592 | 5- (benzo [ d ]]Thiazol-2-yl) -2-chloroanilines | ++++ |
| 593 | 4- (5-tert-butylbenzo [ d ]]Oxazol-2-yl) anilines | +++ |
| 594 | 3- (benzo [ d ]]Thiazol-2-yl) phenol | ++++ |
| 595 | 2- (2, 4-dichlorophenyl) benzo [ d]Thiazoles | ++ |
| 596 | 5- (benzo [ d ]]Thiazol-2-yl) -2-methoxyphenol | ++++ |
| 597 | 5- (benzo [ d ]]Thiazol-2-yl) -2-methoxyaniline | +++ |
| 598 | 2- (3-chlorophenyl) benzo [ d]Oxazolyl-6-amines | +++ |
| 599 | 2- (3-methyl-4-nitrophenyl) benzo [ d]Thiazoles | ++++ |
| 600 | 2- (3-methoxyphenyl) -1H-benzo [ d]Imidazole | ++ |
| 601 | 4- (benzo [ d ]]Thiazol-2-yl) anilines | +++ |
| 602 | 3- (benzo [ d ]]Thiazol-2-yl) anilines | +++ |
| 603 | 2- (3, 4-dimethylphenyl) benzo [ d]Oxazol-5-amines | +++ |
| 604 | 6-nitro-2-phenyl-1H-benzo [ d]Imidazole | +++ |
| 605 | 5-methyl-2- (4-nitrophenyl) -1H-benzo [ d]Imidazole | +++ |
| 606 | 2- (3-methoxyphenyl) benzo [ d]Thiazoles | +++ |
| 607 | 2- (3-methyl-4-nitrophenyl) benzo [ d]Oxazole (oxazole) | ++++ |
| 608 | 2- (benzo [ d ]][1，3]Dioxolen-5-yl) benzo [ d]Thiazoles | ++++ |
| 609 | 4- (5-sec-butylbenzo [ d ]]Oxazol-2-yl) anilines | +++ |
| 610 | 5-amino-2- (5, 6-dimethylbenzo [ d ]]Oxazol-2-yl) phenol | ++++ |
| 611 | 6-methyl-2- (4- (trifluoromethyl) phenyl) benzo [ d]Oxazole (oxazole) | +++ |
| 612 | 5-methyl-2- (thien-2-yl) benzo [ d]Oxazole (oxazole) | ++ |
| 613 | 2-p-tolyl-1H-benzo [ d ]]Imidazole | +++ |
| 614 | 2- (benzo [ d ]][1，3]Dioxolen-5-yloxy) -N- (benzo [ d)]Thiazol-2-yl) acetamide | + |
| 615 | 1-ethyl-2-methyl-N-phenyl-1H-benzo [ d]Imidazole-5-carboxamides | ++++ |
| 616 | N- (benzo [ d ]]Thiazol-2-yl) -2-bromobenzamides | ++++ |
| 617 | 2- (benzo [ d ]]Thiazol-2-ylthio) -1- (piperidin-1-yl) ethaneones | ++++ |
| 618 | N- (benzo [ d ]][1，3]Dioxolen-5-yl) -3-chlorobenzo [ b]Thiophene-2-carboxamides | ++++ |
| 619 | 5- (benzo [ d ]]Oxazol-2-yl) -2-methoxyanilines | ++++ |
| 620 | 5- (1H-benzo [ d ]]Imidazol-2-yl) -2-methylaniline | ++++ |
| 621 | 3-chloro-N- (2-fluorophenyl) benzo [ b]Thiophene-2-carboxamides | ++++ |
| 622 | 3- (5-chlorobenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 623 | N- (3- (5, 6-dimethylbenzo [ d ]]Oxazol-2-yl) phenyl) furan-2-carboxamide | ++++ |
| 624 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -3-methylbutanamide | ++++ |
| 625 | 5- (5-ethylbenzo [ d ]]Oxazol-2-yl) -2-methylaniline | ++++ |
| 626 | N- (benzo [ d ]]Thiazol-2-yl) benzofuran-2-carboxamides | ++++ |
| 627 | 2-chloro-5- (5, 7-dimethylbenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 628 | 3-amino-N- (4-fluorophenyl) -6, 7-dihydro-5H-cyclopentyl [ e]Thiophenone [2, 3-b ]]Pyridine-2-carboxamides | ++++ |
| 629 | 2-bromo-N- (6-fluorobenzo [ d ]]Thiazol-2-yl) benzamides | ++++ |
| 630 | 3- (5-methoxybenzo [ d ]]Oxazol-2-yl) anilines | ++++ |
| 631 | N- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenyl) -2-methylbutanamide | ++++ |
| 632 | 6-methyl-2- (5-methyl-1H-benzo [ d ]]Imidazol-2-yl) thiophenone [2, 3-b]Pyridyl-3-amines | ++++ |
| 633 | 2- (Phenoxymethyl) benzo [ d]Thiazoles | +++ |
| 634 | 1-ethyl-2-methyl-5-phenyl-1H-benzo [ d]Imidazole | +++ |
| 635 | 2-methyl-5- (6-methylbenzo [ d ]]Oxazol-2-yl) anilines | +++ |
| 636 | 2-chloro-5- (5-methylbenzo [ d ]]Oxazol-2-yl) anilines | +++ |
| 637 | 1- (benzo [ d ]]Thiazol-2-yl) -3-p-tolylurea | +++ |
| 638 | N- (4- (6-methylbenzo [ d ]]Thiazol-2-yl) phenyl) nicotinamide | +++ |
| 639 | 2- (Quinolin-2-yl) benzo [ d]Thiazoles | +++ |
| 640 | 2- (4-Methoxybenzylthio) -1H-benzo [ d]Imidazole | +++ |
| 641 | 2-chloro-N- (4- (oxazolo [4, 5-b))]Pyridin-2-yl) phenyl) benzamides | +++ |
| 642 | N- (3- (5-ethylbenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | +++ |
| 643 | 4- (6-methylbenzo [ d ]]Thiazol-2-yl) phenol | +++ |
| 644 | N- (3- (5-methylbenzo [ d ]]Oxazol-2-yl) phenyl) propanamides | +++ |
| 645 | 2- (3-fluoro-4-methoxyphenylmethylthio) -1-methyl-1H-benzo [ d]Imidazole | +++ |
| 646 | 4-chloro-3- (5, 6-dimethylbenzo [ d ]]Oxazol-2-yl) anilines | +++ |
| 647 | 3- (benzo [ d ]]Thiazol-2-yl) -N- (pyridin-4-ylmethyl) aniline | +++ |
| 648 | N- (1H-benzo [ d ]]Imidazol-2-yl) -2-methylbenzamide | +++ |
| 649 | 2- (4-bromo-3-methylphenyl) benzo [ d]Oxazol-5-amines | +++ |
| 650 | 3-amino-4, 6-dimethyl-N-m-tolylthiophenone [2, 3-b]Pyridine-2-carboxamides | +++ |
| 651 | N- (4- (benzo [ d ])]Thiazol-2-yl) phenyl) isobutyramide | +++ |
| 652 | N- (6-methylbenzo [ d ]]Thiazol-2-yl) furan-2-carboxamide | +++ |
| 653 | 5- (1H-benzo [ d ]]Imidazol-2-yl) -2-chloroaniline | +++ |
| 654 | 2- (4H-1, 2, 4-triazol-3-ylthio) -N- (4- (6-methylbenzo [ d ]]Thiazol-2-yl) phenyl) acetyl | +++ |
| Amines as pesticides | ||
| 655 | 4- (4- (1H-benzo [ d ]]Imidazol-2-yl) phenylcarbamoyl) phenylacetate | +++ |
| 656 | 3, 5, 6-trimethyl-N- (pyridin-4-ylmethyl) benzofuran-2-carboxamide | +++ |
| 657 | 2-ethoxy-N- (4- (6-methylbenzo [ d ]]Thiazol-2-yl) phenyl) acetamide | +++ |
| 658 | N- (6-fluorobenzo [ d ]]Thiazol-2-yl) thiophene-2-carboxamides | +++ |
| 659 | 1- (1H-benzo [ d ]]Imidazol-2-yl) -3-methyl-4-phenyl-1H-pyrazol-5-amine | +++ |
| 660 | 3-ethoxy-N- (4- (6-methylbenzo [ d ]]Thiazol-2-yl) phenyl) propionamide | +++ |
| 661 | N- (4- (benzo [ d ])]Thiazol-2-yl) phenyl) cyclopropanecarboxamides | +++ |
| 662 | N- (4- (5-methylbenzo [ d ]]Oxazol-2-yl) phenyl) acetamide | +++ |
| 663 | N- (2-bromo-4-methylphenyl) -2- (1H-indol-3-yl) -2-oxyacetamide | +++ |
| 664 | 4- (6-methylbenzo [ d ]]Thiazol-2-yl) anilines | ++ |
| 665 | N-phenethylbenzofuran-2-carboxamides | ++ |
| 666 | 4-chloro-N- ((1-methyl-1H-benzo [ d)]Imidazol-2-yl) methyl) aniline | ++ |
| 667 | N- (4- (benzo [ d ])]Thiazol-2-yl) phenyl) propionamide | ++ |
| 668 | N- (2-m-tolylbenzo [ d ]]Oxazol-5-yl) propanamides | ++ |
| 669 | N- (1-methyl-1H-benzo [ d ]]Imidazol-2-yl) benzimidazole (benzamidamide) | ++ |
| 670 | 4-methyl-N- (1-methyl-1H-benzo [ d)]Imidazolyl-5-yl) benzamides | ++ |
| 671 | N- (benzo [ d ]]Thiazol-2-yl) -5-bromo-2-chloroanilides | ++ |
| 672 | N- (4- (6-methylbenzo [ d ]]Oxazol-2-yl) phenyl) thiophene-2-carboxamides | ++ |
| 673 | 3-amino-N- (2-fluorophenyl) -6, 7-dihydro-5H-cyclopentyl [ e]Thiophenone [2, 3-b ]]Pyridine-2-carboxamides | ++ |
| 674 | (3- (benzofuran-2-yl) -1-phenyl-1H-pyrazol-4-yl) methanol | ++ |
| 675 | 2- (4-methoxyphenyl) -5-methylbenzo [ d ]]Oxazole (oxazole) | ++ |
| 676 | 4-ethoxy-N- ((1-methyl-1H-benzo [ d)]Imidazol-2-yl) methyl) aniline | ++ |
| 677 | N- (2-chloro-5- (5-methylbenzo [ d ]]Oxazol-2-yl) phenyl) furan-2-carboxamide | ++ |
| 678 | N- (4-methyl-6, 7-dihydro-5H-cyclopentyl [ d ]]Pyrimidin-2-yl) benzo [ d]Oxazolyl-2-amines | ++ |
| 679 | N- (1H-benzo [ d ]]Imidazol-2-yl) -3-chlorobenzamides | ++ |
| 680 | N- (4- (benzo [ d ])]Thiazol-2-yl) phenyl) tetrahydrofuran-2-carboxamide | ++ |
| 681 | 1- (2- (benzo [ d ])]Oxazol-2-ylamino) -4, 6-dimethylpyrimidin-5-yl) ethanone | ++ |
| 682 | N- (4-methylpyrimidin-2-yl) benzo [ d]Oxazolyl-2-amines | ++ |
| 683 | N- (6- (N, N-dimethylsulfonyl) benzo [ d]Thiazol-2-yl) thiophene-2-carboxamides | ++ |
| 684 | 5-bromo-N- (4-hydroxy-3- (5-methylbenzo [ d ]]Oxazol-2-yl) phenyl) nicotinamide | ++ |
| 685 | 2- (1H-1, 2, 4-triazol-3-ylthio) -N- (4- (benzo [ d ] s]Thiazol-2-yl) phenyl) acetamide | ++ |
| 686 | 5- (5-methoxybenzo [ d ]]Oxazol-2-yl) -2-methylaniline | ++ |
| 687 | N- (6- (N-methylsulfonyl) benzo [ d ]]Thiazol-2-yl) thiophene-2-carboxamides | ++ |
| 688 | 2-chloro-N- (4- (5-methylbenzo [ d ]]Thiazol-2-yl) phenyl) -5- (4H-1, 2, 4-triazol-4-yl) benzamide | ++ |
| 689 | N- (2-fluorophenyl) -2- (1H-indol-3-yl) -2-oxyacetamide | ++ |
| 670 | N- (2, 3-dihydrobenzo [ b ]][1，4]Dioxin-6-yl-2- (1H-indazole)Indoxyl-3-yl) -2-oxyacetyl | ++ |
| Amines as pesticides |
Test of
HPLC-UV-MS was performed on a Gilson 321 HPLC using a Gilson 170 DAD and Finnigan AQA mass spectrometer in electrospray ion mode of operation. The HPLC column used was Phenomenex Gemini C18150X 4.6 mm. Preparative HPLC was performed on Gilson 321, with Gilson 170 DAD for detection. Fractions were collected using a Gilson 215 fraction collector. The preparative HPLC column used was Phenomenex Gemini C18150X 10mm and the mobile phase was acetonitrile/water.
Operating Bruker device records at 300MHz1HNMR spectroscopy. In CDCl3NMR spectra were obtained in solution (ppm scale) using chloroform (7.25ppm) or DMSO-D6(2.50ppm) as reference standard. When multiple peaks occur, the following abbreviations are used: s (singlet), d (doublet), t (triplet), m (multiplet), br (broad), dd (doublet of two pairs), dt (doublet of two pairs), td (doublet of three pairs). When given a coupling constant, expressed in hertz (Hz).
Flash chromatography (40-65 μm silica gel) for column chromatography or automatic purification system (C)SP1 (g)TMPurification system). The reaction in the microwave is at Initiator8TM(Biotage). The following abbreviations are used: DMSO (dimethyl sulfoxide), HATU (O- (7-azabenzotriazol-yl) -N, N, N ', N' -tetramethylthiourea hexafluorophosphate), HCl (hydrochloric acid), MgSO4(magnesium sulfate), NaOH (sodium hydroxide), Na2CO3(sodium carbonate), NaHCO3(sodium bicarbonate), STAB (Triacetoxyl group)Sodium borohydride), THF (tetrahydrofuran).
Method 1A (Compound I)
2-phenylbenzo [ d ] oxazol-5-amines
2, 4-diaminophenol hydrochloride (7.88g, 40mmol) and benzoic acid (4.88g, 40mmol) were added simultaneously to polyphosphoric acid at 110 deg.C. The resulting mixture was then heated to 180 ℃ for 3 hours. The solution was then poured into water. The resulting precipitate was collected by filtration and washed with saturated sodium bicarbonate solution. The crude product was recrystallized from ethanol/water to yield 8.15g (97%) of the title compound (lcmrsrt ═ 5.17 min, MH)+211.1)。
1H NMR(DMSO)：8.15-8.12(2H，m)，7.60-7.56(3H，m)，7.42(1H，d，J8.7Hz)，6.89(1H，d，J2.1Hz)，6.68(1H，dd，J8.62.2Hz)，5.12(2H，s)。
All compounds described below were prepared by the same general procedure and purified by trituration, recrystallization or column chromatography.
2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-amine
LCMS RT 8.98 min, MH+279.0；1H NMR(DMSO)：8.26(2H，d，J8.2Hz)，7.88(2H，d，J8.3Hz)，7.40(1H，d，J8.7Hz)，6.84(1H，d，J2.1Hz)，6.66(1H，dd，J8.82.2Hz)，5.13(2H，s)
2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-amine
LCMS RT 8.98 min, MH+282.2；1H NMR(DMSO)：7.89(2H，d，J9.1Hz)，7.30(1H，d，J8.5Hz)，6.80-6.76(3H，m)，6.54(1H，dd，J8.82.2Hz)，4.99(2H，s)，3.42(2H，q，J7.1Hz)，1.14(3H，q，J7.1Hz)
2- (pyridin-3-yl) benzo [ d ] oxazol-5-amines
LCMS RT ═ 6.42 min, MH+212.2；1HNMR(DMSO)：9.29(1H，d，J1.9Hz)，8.77(1H，dd，J4.81.4Hz)，.48-8.44(1H，m)，7.62(1H，dd，J9.04.8Hz)，7.46(1H，d，J8.8Hz)，6.91(1H，d，J2.0Hz)，6.71(1H，dd，J8.72.1Hz)，5.18(2H，s)
2- (5-nitrobenzo [ d ] oxazol-2-yl) phenol
LCMS RT ═ 6.94 min;1H NMR(DMSO)：10.91(1H，s)，8.74(1H，d，J2.3Hz)，8.37(1H，dd，J9.02.4Hz)，8.11-8.04(2H，m)，7.60-7.55(1H，m)，7.18-7.08(2H，m)
2- (5-aminobenzo [ d ] oxazol-2-yl) phenol
LCMS RT ═ 6.08 min, MH+227.2；1H NMR(DMSO)：11.46(1H，s)，8.02(1H，dd，J7.81.6Hz)，7.58-7.53(2H，m)，7.18-7.10(2H，m)，6.96(1H，d，J2.1Hz)，6.77(1H，dd，J8.72.2Hz)，5.29(2H，s)
3- (5-Propylbenzo [ d ] oxazol-2-yl) benzoic acid
LCMS RT 4.58 min MH+282.1；1H NMR(DMSO)：13.44(1H，s)，8.78(1H，s)，8.47(1H，d，J8.0Hz)，8.22(1H，d，J8.4Hz)，7.84-7.74(2H，m)，7.70(1H，s)，7.35(1H，d，J9.0Hz)，2.78-2.73(2H，m)，1.71(2H，q，J7.6Hz)，0.98(3H，d，J7.2Hz)
5-amino-2- (5-aminobenzo [ d ] oxazol-2-yl) phenol
LCMS RT 5.24 min MH+242.2；1H NMR(DMSO)：11.40(1H，s)，7.63(1H，d，J8.6Hz)，7.40(1H，d，J8.7Hz)，6.83(1H，d，J2.1Hz)，6.63(1H，dd，J8.62.3Hz)，6.31(1H，d，J8.42.2Hz)，6.22(1H，d，J1.9Hz)，6.05(2H，s)，5.15(2H，s)
5- (ethylsulfonyl) -2-phenylbenzo [ d ] oxazoles
LCMS RT 5.94 min MH+288.1；1H NMR(DMSO)：8.32(1H，d，J1.3Hz)，8.26(2H，dd，J6.41.6Hz)，8.10(1H，d，J8.5Hz)，7.97(1H，dd，J8.51.7Hz)，7.72-7.64(3H，m)，3.43-3.38(2H，m)，1.14(3H，t，J7.4Hz)
2, 5-biphenylbenzo [ d ] oxazoles
LCMS RT ═ 9.41 min, MH+271.9；1H NMR(DMSO)：8.26-8.23(2H，m)，8.08(1H，d，J1.3Hz)，7.89(1H，d，J8.5Hz)，7.77-7.72(3H，m)，7.68-7.61(3H，m)，7.51(2H，t，J7.7Hz)，7.43-7.38(1H，m)
2-phenylnaphthalene [1, 2-d ] oxazoles
LCMS RT 8.75 min MH+246.2；1HNMR(DMSO)：8.48(1H，d，J8.1Hz)，8.32-8.27(2H，m)，8.14(1H，d，J8.1Hz)，8.01(2H，s)，7.78-7.72(1H，m)，7.68-7.60(4H，m)
2-phenylbenzo [ d ] oxazole-5-carboxylic acid
LCMS RT 4.41 min MH+240.1；1H NMR(DMSO)：13.00(1H，br)，8.33(1H，dd，J1.60.5Hz)，8.26-8.23(2H，m)，8.06(1H，dd，J8.61.7Hz)，7.91(1H，dd，J8.50.5Hz)，7.72-7.62(3H，m)
2- (4-propylphenyl) benzo [ d ] oxazole-5-carboxylic acid
1H NMR(DMSO)：13.10(1H，br)，8.30(1H，dd，J1.50.4Hz)，8.15(2H，d，J8.3Hz)，8.04(1H，dd，J8.61.7Hz)，7.88(1H，d，J8.5Hz)，7.47(2H，d，J8.4Hz)，2.68(2H，t，J8.0Hz)，1.70-1.62(2H，m)，0.93(3H，t，J7.5Hz)
2- (4-propylphenyl) benzo [ d ] oxazole-6-carboxylic acid
1HNMR(DMSO)：13.10(1H，br)，8.27(1H，dd，J1.50.5Hz)，8.16(2H，d，J8.3Hz)，8.02(1H，dd，J8.31.5Hz)，7.88(1H，dd，J8.30.5Hz)，7.48(2H，d，J8.4Hz)，2.68(2H，t，J8.0Hz)，1.72-1.58(2H，m)，0.93(3H，t，J7.5Hz)
5-chloro-2-phenylbenzo [ d ] oxazoles
LCMS RT 8.61 min MH+230.1；1H NMR(DMSO)：8.21(2H，dd，J7.61.4Hz)，7.94(1H，d，J2.1Hz)，7.86(1H，d，J8.7Hz)，7.72-7.60(3H，m)，7.49(1H，dd，J8.72.1Hz)
6-chloro-2-phenylbenzo [ d ] oxazoles
LCMS RT ═ 9.00 min, MH+230.1；1HNMR(DMSO)：8.22-8.18(2H，m)，8.02(1H，d，J1.9Hz)，7.84(1H，d，J8.5Hz)，7.70-7.60(3H，m)，7.48(1H，dd，J8.52.0Hz)
5-tert-butyl-2-phenylbenzo [ d ] oxazoles
LCMS RT ═ 9.82 min, MH+252.0；1H NMR(DMSO)：7.72-7.70(4H，m)，7.59(2H，dt，J7.61.0Hz)，7.46-7.40(2H，m)，1.38(9H，s)
6-nitro-2-phenylbenzo [ d ] oxazoles
LCMS RT ═ 7.30 min;1H NMR(DMSO)：8.77-8.76(1H，m)，8.34(1H，d，J8.8Hz)，8.27(2H，d，J7.7Hz)，8.05(1H，d，J8.8Hz)，7.80-7.65(3H，m)
4- (5-chlorobenzo [ d ] oxazol-2-yl) -N, N-diethylaniline
LCMS RT ═ 10.17 min, MH+301.1；1H NMR(DMSO)：8.03(2H，d，J8.9Hz)，7.82-7.76(2H，m)，7.40(1H，dd，J8.62.0Hz)，6.89(2H，d，J8.9Hz)
4- (6-chlorobenzo [ d ] oxazol-2-yl) -N, N-diethylaniline
LCMS RT ═ 10.28 min, MH+301.0；1HNMR(DMSO)：7.95(2H，d，J9.1Hz)，7.87(1H，d，J1.7Hz)，7.67(1H，d，J8.4Hz)，7.38(1H，dd，J8.42.1Hz)，6.83(2H，d，J9.1Hz)，3.45(4H，q，J7.2Hz)，1.15(6H，t，J7.1Hz)
4- (5-tert-butylbenzo [ d ] oxazol-2-yl) -N, N-diethylaniline
LCMS RT ═ 13.81 minutes, MH+323.2；1H NMR(DMSO)：7.94(2H，d，J9.3Hz)，7.66(1H，d，J1.5Hz)，7.58(1H，d，J8.6Hz)，7.36(1H，dd，J8.61.9Hz)，6.82(2H，d，J9.2Hz)，3.44(4H，q，J7.0Hz)，1.35(9H，s)，1.15(6H，t，J7.1Hz)
4- (benzo [ d ] oxazol-2-yl) -N, N-diethylaniline
LCMS RT ═ 10.50 min, MH+267.0；1H NMR(DMSO)：7.97(2H，d，J9.1Hz)，7.71-7.64(2H，m)，7.36-7.30(2H，m)，6.82(2H，d，J9.2Hz)，3.44(4H，q，J7.0Hz)，1.15(6H，t，J7.1Hz)
N, N-diethyl-4- (5- (ethylsulfonyl) benzo [ d ] oxazol-2-yl) aniline
LCMS RT 7.45 min MH+358.9；1HNMR(DMSO)：8.13(1H，dd，J1.30.4Hz)，8.00(2H，d，J9.1Hz)，7.95(1H，dd，J8.10.4Hz)，7.83(1H，dd，J8.41.8Hz)，6.85(2H，d，J9.2Hz)，3.50-3.39(6H，m)，1.23-1.04(9H，m)
N, N-diethyl-4- (5-phenylbenzo [ d ] oxazol-2-yl) aniline
LCMS RT 15.22 min, MH+343.1；1H NMR(DMSO)：7.99(2H，d，J8.9Hz)，7.93(1H，s)，7.77-7.71(3H，m)，7.60(1H，d，J8.3Hz)，7.52-7.46(2H，m)，7.40-7.35(1H，m)，6.84(2H，d，J9.0Hz)，3.44(4H，q，J7.0Hz)，1.15(6H，t，J7.1Hz)
N, N-diethyl-4- (naphtho [ l, 2-d ] oxazol-2-yl) aniline
LCMS RT 11.21 min, MH+317.1；1H NMR(DMSO)：8.41(1H，d，J8.3Hz)，8.12-8.02(3H，m)，7.94-7.86(2H，m)，7.72-7.66(1H，m)，7.60-7.55(1H，m)，6.85(2H，d，J9.0Hz)，3.44(4H，q，J7.0Hz)，1.15(6H，t，J7.1Hz)
2- (pyridin-2-yl) benzo [ d ] oxazoles
LCMS RT 5.68 min MH+197.0；1H NMR(DMSO)：8.87(1H，d，J4.4Hz)，8.41(1H，d，J8.0Hz)，8.14(1H，dt，J7.81.5Hz)，7.93(2H，t，J7.4Hz)，7.73-7.69(1H，m)，7.60-7.50(2H，m)
2- (4- (piperidin-1-yl) phenyl) benzo [ d ] oxazol-5-amine
LCMS RT ═ 6.95 min, MH+206.1；1H NMR(DMSO)：7.92(2H，d，J9.0Hz)，7.32(1H，d，J9.0Hz)，7.05(2H，d，J9.0Hz)，6.80(1H，d，J2.1Hz)，6.58(1H，dd，J8.02.0Hz)，5.01(2H，s)，1.60(6H，m)
2- (4- (4-methylpiperazin-1-yl) phenyl) benzo [ d ] oxazol-5-amine
LCMS RT 5.34 min MH+309.1；1H NMR(DMSO)：7.94(2H，d，J9.0Hz)，7.33(1H，d，J9.0Hz)，7.08(2H，d，J9.0Hz)，6.80(1H，d，J2.1Hz)，6.58(1H，dd，J8.02.0Hz)，5.03(2H，s)，2.60-2.57(4H，m)，2.45-2.42(4H，m)，2.23(3H，s)
2- (4- (diethylamino) phenyl) benzo [ d ] oxazole-5-carboxylic acid
1H NMR(DMSO)：13.00(1H，br)，8.17(1H，d，J1.5Hz)，7.99(2H，d，J9.0Hz)，7.94(1H，dd，J8.51.7Hz)，7.77(1H，d，J8.4Hz)，6.84(2H，d，J9.1Hz)，3.45(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
2-propylbenzo [ d ] oxazol-5-amine
LCMS RT ═ 6.81 minutes, MH+177.2；1H NMR(DMSO)：7.26(1H，d，J8.6Hz)，6.76(1H，d，J2.2Hz)，6.57(1H，dd，J8.62.2Hz)，4.98(2H，s)，2.80(2H，t，J7.3Hz)，1.81-1.70(2H，m)，0.96(3H，t，J7.4Hz)
2-p-tolyloxazolo [5, 4-b ] pyridine
LCMS RT ═ 6.72 min, MH+211.1；1H NMR(DMSO)：8.38(1H，dd，J5.01.5Hz)，8.26(1H，dd，J7.91.6Hz)，8.14(2H，d，J8.2Hz)，7.53-7.45(3H，m)，2.44(3H，s)
2-p-tolyloxazolo [4, 5-b ] pyridine
LCMS RT ═ 6.12 min, MH+211.1；1H NMR(DMSO)：8.54(1H，dd，J4.91.4Hz)，8.23(1H，dd，J8.21.4Hz)，8.16(2H，d，J8.2Hz)，7.59-7.44(3H，m)，2.44(3H，s)
2- (4-morpholinophenyl) benzo [ d ] oxazol-5-amine
LCMS RT 5.52 min MH+295.8；1H NMR(DMSO)：7.97(2H，d，J9.0Hz)，7.33(1H，d，J9.0Hz)，7.09(2H，d，J9.0Hz)，6.81(1H，d，J2.1Hz)，6.59(1H，dd，J8.02.0Hz)，5.04(2H，s)，3.77-3.74(4H，m)，3.29-3.24(4H，m)
5-phenyl-2-p-tolylbenzo [ d ] oxazole
LCMS RT ═ 10.00 min, MH+286.1；1H NMR(DMSO)：8.12(2H，d，J8.5Hz)，8.06(1H，d，J1.8Hz)，7.86(1H，d，J8.6Hz)，7.77-7.70(3H，m)，7.53-7.37(5H，m)，2.43(3H，s)
2- (4-chlorophenyl) -5-phenylbenzo [ d ] oxazole
LCMS RT ═ 10.54 min, MH+306.0；1H NMR(DMSO)：8.24(2H，d，J8.6Hz)，8.09(1H，d，J1.8Hz)，7.89(1H，d，J8.6Hz)，7.77-7.70(5H，m)，7.53-7.34(3H，m)
2-cyclohexyl-5-nitrobenzo [ d ] oxazoles
LCMS RT 7.90 min MH+247.3；1H NMR(CDCl3)：8.62(1H，d，J2.2Hz)，8.33(1H，dd，J8.92.3Hz)，7.63(1H，d，J8.9Hz)，3.11-3.01(1H，m)，2.27-2.21(2H，m)，1.98-1.92(2H，m)，1.84-1.71(3H，m)，1.57-1.37(3H，m)
5-tert-butyl-2-p-tolylbenzo [ d ] oxazole
LCMS RT ═ 10.53 min, MH+266.1；1H NMR(DMSO)：8.08(2H，d，J8.2Hz)，7.78(1H，d，J1.6Hz)，7.68(1H，d，J8.6Hz)，7.48(1H，dd，J8.72.0Hz)，7.43(2H，d，J8.0Hz)，2.42(3H，s)，1.37(9H，s)
2-p-tolylbenzo [ d ] oxazole
LCMS RT 7.82 min MH+210.1；1H NMR(DMSO)：8.11(2H，d，J8.2Hz)，7.81-7.76(2H，m)，7.46-7.40(4H，m)，2.42(3H，s)
2- (3- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-amine
LCMS RT ═ 6.39 min, MH+279.0；1H NMR(DMSO)：8.41(1H，d，J8.0Hz)，8.37(1H，s)，7.98(1H，d，J8.0Hz)，7.84(1H，t，J8.0Hz)，7.46(1H，d，J8.9Hz)，6.91(1H，d，J1.9Hz)，6.72(1H，d，J8.62.0Hz)，5.18(2H，s)
5- (ethylsulfonyl) -2-p-tolylbenzo [ d ] oxazole
LCMS RT ═ 6.46 min, MH+302.0；1H NMR(DMSO)：8.28(1H，d，J1.6Hz)，8.14(2H，d，J8.2Hz)，8.06(1H，d，J8.6Hz)，7.94(1H，dd，J8.61.7Hz)，7.47(2H，d，J8.1Hz)，3.42-3.34(2H，m)，2.44(3H，s)，1.12(3H，t，J7.3Hz)
2- (4-chlorophenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT ═ 6.63 min, MH+322.1；1H NMR(CDCl3)：8.39(1H，d，J1.7Hz)，8.27(2H，d，J8.7Hz)，8.00(1H，dd，J8.51.8Hz)，7.80(1H，d，J8.5Hz)，7.60(2H，d，J8.6Hz)，3.23(2H，q，J7.6Hz)，1.36(3H，t，J7.4Hz)
4-nitro-2-p-tolylbenzo [ d ] oxazole
LCMS RT ═ 6.97 min, MH+255.0；1H NMR(DMSO)：8.27(1H，dd，J8.10.8Hz)，8.23(1H，dd，J8.20.8Hz)，8.18(2H，d，J8.2Hz)，7.65(1H，t，J8.2Hz)，7.49(2H，d，J8.0Hz)，2.45(3H，s)
6-nitro-2-p-tolylbenzo [ d ] oxazole
LCMS RT 7.83 min, MH+255.0；1H NMR(DMSO)：8.74(1H，d，J2.2Hz)，8.33(1H，dd，J8.72.2Hz)，8.17(2H，d，J8.2Hz)，8.02(1H，d，J8.8Hz)，7.49(2H，d，J7.9Hz)，2.45(3H，s)
2- (4-chlorophenyl) -6-nitrobenzo [ d ] oxazole
LCMS RT 7.76 min;1H NMR(DMSO)：8.77(1H，d，J2.2Hz)，8.35(1H，dd，J8.72.2Hz)，8.27(2H，d，J8.2Hz)，8.06(1H，d，J8.8Hz)，7.76(2H，d，J7.9Hz)
2-p-tolyloxazolo [4, 5-c ] pyridine
LCMS RT ═ 6.24 min, MH+211.0；1H NMR(DMSO)：9.11(1H，d，J0.9Hz)，8.59(1H，d，J5.6Hz)，8.14(2H，d，J8.2Hz)，7.90(1H，dd，J5.61.0Hz)，7.47(2H，d，J8.0Hz)，2.44(3H，s)
2-m-tolylbenzo [ d ] oxazol-5-amine
LCMS RT ═ 6.18 min, MH+225.0；1H NMR(DMSO)：7.97-7.91(2H，m)，7.50-7.39(3H，m)，6.87(1H，d，J2.0Hz)，6.67(1H，dd，J8.72.2Hz)，5.11(2H，s)，2.42(3H，s)
2- (3- (dimethylamino) phenyl) benzo [ d ] oxazol-5-amine
LCMS RT ═ 6.12 min, MH+254.0；1H NMR(DMSO)：7.48-7.31(4H，m)，6.96-6.92(1H，m)，6.87(1H，d，J2.2Hz)，6.66(1H，dd，J8.62.2Hz)，5.09(2H，s)，3.00(6H，s)
5-bromo-2-p-tolylbenzo [ d ] oxazole
LCMS RT ═ 9.41 min, MH+289.8；1H NMR(DMSO)：8.10(2H，d，J8.2Hz)，8.04(1H，d，J1.9Hz)，7.78(1H，d，J8.6Hz)，7.58(1H，dd，J8.72.0Hz)，7.45(2H，d，J8.0Hz)，2.43(3H，s)
2-o-tolylbenzo [ d ] oxazol-5-amine
LCMS RT ═ 6.16 min, MH+225.0；1H NMR(DMSO)：8.05(1H，d，J7.7Hz)，7.53-7.37(4H，m)，6.90(1H，d，J2.2Hz)，6.68(1H，dd，J8.72.2Hz)，5.10(2H，s)，2.71(3H，s)
2- (2-chlorophenyl) benzo [ d ] oxazol-5-amine
LCMS RT 4.31 min MH+245.0；1H NMR(DMSO)：8.10(1H，d，J7.3Hz)，7.75-7.52(3H，m)，7.45(1H，d，J8.6Hz)，6.92(1H，d，J1.6Hz)，6.73(1H，dd，J8.82.1Hz)，5.16(2H，s)
6-bromo-2-p-tolyloxazolo [5, 4-b ] pyridine
LCMS RT 8.40 min MH+288.8；1H NMR(DMSO)：8.59(1H，d，J2.1Hz)，8.50(1H，d，J2.2Hz)，8.13(2H，d，J8.2Hz)，7.48(2H，d，J8.0Hz)
5, 6-dimethyl-2-p-tolylbenzo [ d ] oxazole
LCMS RT 8.76 min MH+238.0；1H NMR(DMSO)：8.06(2H，d，J8.2Hz)，7.56(2H，s)，7.41(2H，d，J8.2Hz)，2.41(3H，s)，2.35(3H，s)，2.33(3H，s)
2- (4-chlorophenyl) -5, 6-dimethylbenzo [ d ] oxazole
LCMS RT ═ 9.07 min, MH+258.0；1H NMR(DMSO)：8.19(2H，d，J8.6Hz)，7.69(2H，d，J8.6Hz)，7.60(2H，s)，2.38(3H，s)，2.36(3H，s)
2- (2, 4-dichlorophenyl) -5, 6-dimethylbenzo [ d ] oxazole
LCMS RT ═ 9.68 min, MH+291.9；1H NMR(DMSO)：8.16(1H，d，J8.5Hz)，7.90(1H，d，J2.1Hz)，7.69-7.61(3H，m)，2.38(3H，s)，2.36(3H，s)
2- (3-fluorophenyl) benzo [ d ] oxazol-5-amine
LCMS RT ═ 9.45 min, MH+229.1；1H NMR(DMSO)：7.98(1H，d，J8.0Hz)，7.89-7.84(1H，m)，7.68-7.60(1H，m)，7.48-7.42(2H，m)，6.89(1H，d，J2.1Hz)，6.71(1H，dd，J8.72.2Hz)，5.15(2H，s)
2- (5-butylpyridin-2-yl) -6-nitrobenzo [ d ] oxazoles
LCMS RT 7.34 min MH+298.0；1H NMR(DMSO)：8.81(1H，d，J2.1Hz)，8.71(1H，d，J1.5Hz)，8.37-8.32(2H，m)，8.08(1H，d，J8.8Hz)，7.95(1H，dd，J8.12.1Hz)，2.75(2H，t，J7.6Hz)，1.70-1.59(2H，m)，1.41-1.29(2H，m)，0.93(3H，t，J7.3Hz)
2- (4-chlorophenyl) -5- (isopropylsulfone) benzo [ d ] oxazole
LCMS RT ═ 6.98 min;1H NMR(DMSO)：8.29-8.24(3H，m)，8.09(1H，d，J8.6Hz)，7.94(1H，dd，J8.61.7Hz)，7.74(2H，d，J8.6Hz)，3.56-3.50(1H，m)，1.19(6H，d，J6.8Hz)
5-bromo-2- (4-chlorophenyl) benzo [ d ] oxazole
LCMS RT ═ 9.09 min, MH+307.9；1H NMR(DMSO)：8.21(2H，d，J8.7Hz)，8.08(1H，d，J1.9Hz)，7.80(1H，d，J8.7Hz)，7.71(2H，d，J8.7Hz)，7.62(1H，dd，J8.72.0Hz)
4- (5-chlorobenzo [ d ] oxazol-2-yl) aniline
LCMS RT 6.48 min MH+244.9；1H NMR(DMSO)：7.86(2H，d，J8.5Hz)，7.74(1H，d，J2.1Hz)，7.70(1H，d，J8.6Hz)，7.34(1H，dd，J8.82.1Hz)，6.70(2H，d，J8.7Hz)，6.06(2H，s)
4- (6-chlorobenzo [ d ] oxazol-2-yl) aniline
LCMS RT＝6.57 min, MH+245.0；1H NMR(DMSO)：7.87-7.82(3H，m)，7.66(1H，d，J8.5Hz)，7.37(1H，dd，J8.72.0Hz)，6.70(2H，d，J8.8Hz)，6.04(2H，s)
2- (3-chlorophenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 6.78 min;1H NMR(DMSO)：8.34(1H，d，J1.3Hz)，8.23-8.20(2H，m)，8.10(1H，d，J8.6Hz)，7.99(1H，dd，J8.61.8Hz)，7.80-7.76(1H，m)，7.72-7.67(1H，m)，3.40(2H，q，J7.3Hz)，1.13(3H，t，J7.3Hz)
2- (2-chlorophenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT ═ 6.37 minutes;1H NMR(DMSO)：8.39(1H，d，J1.6Hz)，8.20(1H，dd，J7.61.7Hz)，8.12(1H，d，J8.6Hz)，8.01(1H，dd，J8.61.8Hz)，7.78-7.60(3H，m)，1.14(3H，t，J7.3Hz)
2- (3, 4-dichlorophenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 7.25 min;1H NMR(DMSO)：8.39(1H，d，J2.0Hz)，8.35(1H，d，J1.4Hz)，8.19(1H，dd，J8.42.0Hz)，8.10(1H，d，J8.6Hz)，7.99(1H，dd，J8.61.8Hz)，7.94(1H，d，J8.4Hz)，3.41(2H，q，J7.3Hz)，1.13(3H，t，J7.3Hz)
2- (2, 3-dichlorophenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT ═ 6.80 minutes;1H NMR(DMSO)：8.42(1H，d，J1.80.6Hz)，8.17-8.13(2H，m)，8.05-7.96(2H，m)，7.65(1H，t，J8.0Hz)，3.41(2H，q，J7.3Hz)，1.14(3H，t，J7.3Hz)
2- (1-phenylethyl) benzo [ d ] oxazol-5-amine
LCMS RT ═ 5.80 min, MH+239.0；1H NMR(DMSO)：7.35-7.23(6H，m)，6.80(1H，d，J2.1Hz)，6.57(1H，dd，J8.62.2Hz)，5.02(2H，s)，4.42(1H，q，J7.1Hz)，1.66(3H，d，J7.2Hz)
2- (4-chlorophenyl) benzo [ d ] oxazole-5-sulfonic acid
LCMS RT 4.44 min MH+309.9；1H NMR(DMSO)：8.28(2H，d，J8.7Hz)，8.03(1H，s)，7.83-7.73(4H，m)
5-chloro-2- (pyridin-4-yl) benzo [ d ] oxazole
LCMS RT ═ 6.51 min, MH+231.0；1HNMR(DMSO)：8.87(2H，d，J8.6Hz)，8.11(2H，d，J6.1Hz)，8.04(1H，d，J1.8Hz)，7.92(1H，d，J8.8Hz)，7.57(1H，dd，J8.72.1Hz)
6-chloro-2- (pyridin-4-yl) benzo [ d ] oxazole
LCMS RT ═ 6.49 min, MH+231.0；1HNMR(DMSO)：8.87(2H，d，J6.1Hz)，8.10-8.08(3H，m)，7.93(1H，d，J8.6Hz)，7.54(1H，dd，J8.62.0Hz)
4- (5-bromobenzo [ d ] oxazol-2-yl) aniline
LCMS RT ═ 6.70 min, MH+289.2；1H NMR(DMSO)：7.88-7.83(3H，m)，7.66(1H，d，J8.6Hz)，7.46(1H，dd，J8.62.1Hz)，6.69(2H，d，J8.8Hz)，6.09(2H，s)
2- (4-chlorophenyl) -5- (methylsulfonyl) benzo [ d ] oxazole
LCMS RT ═ 6.43 minutes, MH+308.2；1H NMR(CDCl3)：8.43(1H，dd，J1.80.3Hz)，8.28(2H，d，J8.7Hz)，8.05(1H，dd，J8.61.9Hz)，7.81(1H，dd，J8.50.4Hz)，7.61(2H，d，J8.8Hz)，3.18(3H，s)
2- (4-chlorophenyl) -5- (propylsulfonyl) benzo [ d ] oxazole
LCMS RT 7.09 min, MH+335.9；1H NMR(CDCl3)：8.38(1H，dd，J1.70.4Hz)，8.27(2H，d，J8.8Hz)，8.00(1H，dd，J8.51.8Hz)，7.80(1H，dd，J8.50.4Hz)，7.60(2H，d，J8.8Hz)，3.21-3.15(2H，m)，1.89-1.76(2H，m)，1.05(3H，t，J7.4Hz)
2- (Yl-1-Yl) benzo [ d ] oxazol-5-Amines
LCMS RT ═ 6.59 min, MH+261.1；1H NMR(DMSO)：9.41(1H，d，J8.6Hz)，8.38(1H，dd，J7.31.0Hz)，8.19(1H，d，J8.2Hz)，8.09(1H，dd，J7.80.9Hz)，7.79-7.64(3H，m)，7.49(1H，d，J8.7Hz)，6.99(1H，d，J2.1Hz)，6.74(1H，d，J8.72.2Hz)，5.17(2H，s)
2- (biphenyl-4-yl) benzo [ d ] oxazol-5-amines
LCMS RT ═ 6.92 minutes, MH+287.1；1H NMR(DMSO)：8.22(2H，d，J8.2Hz)，7.90(2H，d，J8.3Hz)，7.81-7.76(2H，m)，7.53(2H，t，J7.8Hz)，7.47-7.41(2H，m)，6.90(1H，d，J2.2Hz)，6.69(1H，d，J8.62.2Hz)，5.14(2H，s)
2- (quinolin-2-yl) benzo [ d ] oxazol-5-amines
LCMS RT 5.78 min, MH+262.1；1H NMR(DMSO)：8.60(1H，d，J8.7Hz)，8.39(1H，d，J8.6Hz)，8.19(1H，dd，J8.30.5Hz)，8.10(1H，dd，J8.40.8Hz)，7.92-7.86(1H，m)，7.76-7.70(1H，m)，7.56(1H，d，J8.7Hz)，6.97(1H，d，J2.1Hz)，6.79(1H，dd，J8.72.2Hz)，5.22(2H，s)
2- (quinolin-3-yl) benzo [ d ] oxazol-5-amines
LCMS RT 5.76 min MH+262.1；1H NMR(DMSO)：9.58(1H，d，J2.1Hz)，8.14(1H，d，J2.0Hz)，8.24(1H，dd，J7.80.8Hz)，8.13(1H，d，J8.3Hz)，7.93-7.88(1H，m)，7.74(1H，td，J8.00.9Hz)，7.49(1H，d，J8.6Hz)，6.95(1H，d，J2.1Hz)，6.74(1H，dd，J8.72.2Hz)，5.20(2H，s)
2- (6-methoxynaphthalen-2-yl) benzo [ d ] oxazol-5-amines
LCMS RT 6.56 min MH+291.1；1H NMR(DMSO)：8.67(1H，d，J1.3Hz)，8.16(1H，dd，J8.61.7Hz)，8.07(1H，d，J9.1Hz)，7.99(1H，d，J8.8Hz)，7.45-7.42(2H，m)，7.27(1H，dd，J8.72.5Hz)，6.90(1H，d，J2.0Hz)，6.68(1H，dd，J8.62.2Hz)，5.12(2H，s)，3.92(3H，s)
2- (6-bromonaphthalen-2-yl) benzo [ d ] oxazol-5-amines
LCMS RT 7.59 min MH+339.3；1H NMR(DMSO)：8.78(1H，s)，8.34(1H，d，J1.7Hz)，8.26(1H，d，J8.61.6Hz)，8.14(1H，d，J8.9Hz)，8.09(1H，d，J8.7Hz)，7.76(1H，dd，J8.92.0Hz)，7.46(1H，d，J8.7Hz)，6.92(1H，d，J2.2Hz)，6.72(1H，dd，J8.62.2Hz)，5.16(2H，s)
2- (4-chlorophenyl) naphtho [ l, 2-d ] oxazole
LCMS RT ═ 9.55 min, MH+280.1；1H NMR(DMSO)：8.47(1H，dd，J8.20.6Hz)，8.29(2H，d，J8.7Hz)，8.17-8.13(1H，m)，8.02(2H，s)，7.78-7.70(3H，m)，7.67-7.61(1H，m)
1- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) propan-1-one
LCMS RT 7.92 min MH+286.1；1H NMR(DMSO)：8.44(1H，dd，J1.70.4Hz)，8.24(2H，d，J8.7Hz)，8.09(1H，dd，J8.61.7Hz)，7.93(1H，dd，J8.60.4Hz)，7.73(2H，d，J8.8Hz)，3.17(2H，q，J7.2Hz)，1.13(3H，t，J7.1Hz)
1- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) ethaneone
LCMS RT 7.27 min MH+271.7；1H NMR(DMSO)：8.44(1H，dd，J1.70.4Hz)，8.24(2H，d，J8.8Hz)，8.08(1H，dd，J8.61.7Hz)，7.93(1H，dd，J8.50.5Hz)，7.73(2H，d，J8.8Hz)，2.69(3H，s)
2- (4-cyclohexylphenyl) benzo [ d ] oxazol-5-amine
LCMS RT 8.15 min, MH+293.1；1H NMR(DMSO)：8.05(2H，d，J8.4Hz)，7.45-7.38(3H，m)，6.86(1H，d，J2.0Hz)，6.65(1H，dd，J8.82.2Hz)，5.10(2H，s)，2.64-2.56(1H，m)，1.83-1.70(5H，m)，1.51-1.23(5H，m)
5- (ethylsulfonyl) -2- (quinolin-2-yl) benzo [ d ] oxazole
LCMS RT ═ 6.14 min, MH+339.1；1H NMR(DMSO)：8.69(1H，dd，J8.52.2Hz)，8.52-8.43(2H，m)，8.28-8.21(2H，m)，8.16(1H，d，J8.1Hz)，8.09-8.04(1H，m)，7.97-7.90(1H，m)，7.82-7.76(1H，m)，3.48-3.38(2H，m)，1.15(3H，td，J7.31.3Hz)
5- (ethylsulfonyl) -2- (quinolin-3-yl) benzo [ d ] oxazole
LCMS RT ═ 6.05 min, MH+339.1；1H NMR(DMSO)：9.65(1H，d，J2.1Hz)，9.31(1H，d，J2.1Hz)，8.40(1H，d，J1.8Hz)，8.31(1H，d，J8.1Hz)，8.17(2H，dd，J8.32.2Hz)，8.02(1H，dd，J8.71.8Hz)，8.00-7.93(1H，m)，7.82-7.76(1H，m)，3.43(2H，q，J7.3Hz)，1.15(3H，t，J7.5Hz)
2- (6-bromo-2-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 7.86 min MH+418.0；1H NMR(DMSO)：8.95(1H，m)，8.39-8.33(3H，m)，8.21(1H，d，J9.0Hz)，8.17(1H，d，J8.9Hz)，8.13(1H，dd，J8.50.5Hz)，7.99(1H，dd，J8.61.8Hz)，7.81(1H，dd，J8.71.9Hz)，3.41(2H，q，J7.3Hz)，1.15(3H，t，J7.5Hz)
2- (4-cyclohexylphenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 8.56 min,1H NMR(DMSO)：8.29(1H，dd，J1.80.4Hz)，8.17(2H，d，J8.3Hz)，8.07(1H，dd，J8.60.5Hz)，7.94(1H，dd，J8.51.8Hz)，7.51(2H，d，J8.4Hz)，3.39(2H，q，J7.3Hz)，2.74-2.60(1H，m)，1.84-1.71(5H，m)，1.53-1.24(5H，m)，1.13(3H，t，J7.5Hz)
2- (biphenyl-4-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMSRT 7.31 min, MH+364.1；1H NMR(DMSO)：8.36-8.32(3H，m)，8.11(1H，dd，J8.60.5Hz)，8.00-7.95(3H，m)，7.84-7.79(2H，m)，7.57-7.43(3H，m)，3.41(2H，q，J7.3Hz)，1.14(3H，t，J7.5Hz)
5- (ethylsulfonyl) -2- (yl-1-yl) benzo [ d ] oxazole
LCMS RT 7.03 min, MH+338.1；1H NMR(DMSO)：9.41(1H，d，J8.8Hz)，8.52(1H，dd，J7.21.2Hz)，8.44(1H，d，J1.7Hz)，8.30(1H，d，J8.3Hz)，8.17-8.12(2H，m)，8.02(1H，dd，J8.61.8Hz)，7.84-7.68(3H，m)，3.43(2H，q，J7.3Hz)，1.15(3H，t，J7.5Hz)
5- (ethylsulfonyl) -2- (6-fluoro-2-yl) benzo [ d ] oxazole
LCMS RT 7.29 min MH+356.1；1H NMR(DMSO)：8.97(1H，m)，8.37-8.32(3H，m)，8.17(1H，d，J8.9Hz)，8.12(1H，d，J8.6Hz)，7.99(1H，dd，J8.61.6Hz)，7.89(1H，dd，J10.02.0Hz)，7.61(1H，td，J8.72.0Hz)，3.41(2H，q，J7.3Hz)，1.14(3H，t，J7.5Hz)
2- (benzo [ b ] thiophen-5-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 6.77 min, MH+344.1；1H NMR(CDCl3)：8.70(1H，d，J1.2Hz)，8.27(1H，dd，J1.80.4Hz)，8.18(1H，dd，J8.51.5Hz)，7.99(1H，d，J8.6Hz)，7.88(1H，dd，J8.51.8Hz)，7.70(1H，dd，J8.50.4Hz)，7.52(1H，d，J5.5Hz)，7.43(1H，dd，J5.50.6Hz)，3.12(2H，q，J7.4Hz)，1.25(3H，t，J7.4Hz)
5-amino-2- (5, 6-dichlorobenzo [ d ] oxazol-2-yl) phenol
LCMS RT 7.83 min, MH+295.1；1H NMR(DMSO)：10.88(1H，s)，8.19(1H，s)，8.06(1H，s)，7.69(1H，d，J8.7Hz)，6.35(1H，dd，J8.72.1Hz)，6.29(2H，br)，6.24(1H，d，J2.1Hz)
2- (3, 4-dichlorophenyl) -5- (isopropylsulfonyl) benzo [ d ] oxazole
LCMS RT 7.68 min;1H NMR(DMSO)：8.41(1H，d，J2.0Hz)，8.31(1H，dd，J1.80.4Hz)，8.21(1H，dd，J8.42.0Hz)，8.11(1H，dd，J8.60.5Hz)，7.98-7.93(2H，m)，3.59-3.50(1H，m)，1.19(6H，d，J6.8Hz)
n- (4- (5, 6-dimethylbenzo [ d ] oxazol-2-yl) -3-hydroxyphenyl) acetamide
LCMS RT ═ 6.70 min, MH+263.1；1H NMR(DMSO)：10.83(1H，s)，8.02(1H，dd，J9.96.9Hz)，7.85(1H，dd，J10.47.5Hz)，7.62(1H，d，J8.6Hz)，6.29(1H，dd，J8.72.1Hz)，6.18(1H，d，J2.0Hz)，6.15(2H，br)
4- (5, 6-dichlorobenzo [ d ] oxazol-2-yl) aniline
LCMS RT 7.27 min MH+279.0；1H NMR(DMSO)：8.10(1H，s)，7.97(1H，s)，7.85(2H，d，J8.7Hz)，6.70(2H，d，J8.8Hz)，6.14(2H，s)
5- (ethylsulfonyl) -2- (5, 6, 7, 8-tetrahydronaphthalen-2-yl) benzo [ d ] oxazole
LCMS RT 7.71 min MH+342.2；1H NMR(CDCl3)：8.03(1H，dd，J1.80.5Hz)，7.93-7.87(2H，m)，7.85(1H，dd，J8.51.8Hz)，7.65(1H，dd，J8.5
0.5Hz)，7.23-7.15(1H，m)，3.11(2H，q，J7.4Hz)，2.85-2.76(4H，m)，1.81-1.76(4H，m)，1.24(3H，t，J7.3Hz)
5-amino-2- (5- (ethylsulfonyl) benzo [ d ] oxazol-2-yl) phenol
LCMS RT ═ 5.99 min, MH+319.2；1H NMR(DMSO)：10.88(1H，s)，8.16(1H，dd，J1.80.5Hz)，7.97(1H，dd，J8.50.5Hz)，7.84(1H，dd，J8.41.9Hz)，7.69(1H，d，J8.6Hz)，6.31(1H，dd，J8.72.1Hz)，6.24(2H，s)，6.20(1H，d，J2.1Hz)，3.37(2H，q，J7.5Hz)，1.12(3H，t，J7.3Hz)
Method 1A (Compound Ic)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) nicotinamide
LCMS RT 4.64 min MH+317.1；1H NMR(DMSO)：10.67(1H，s)，9.37(1H，d，J1.5Hz)，9.16(1H，d，J1.6Hz)，8.84-8.78(2H，m)，8.56(1H，dt，J8.01.7Hz)，8.36-8.32(2H，m)，7.86(1H，d，J8.8Hz)，7.80(1H，dd，J8.92.0Hz)，7.70-7.58(2H，m)
4-methoxy-N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) benzamide
1HNMR(DMSO)：10.25(1H，s)，8.23(1H，s)，8.16(2H，d，J8.9Hz)，8.00(2H，d，J8.9Hz)，7.72(2H，s)，7.17(2H，d，J9.0Hz)，7.09(2H，d，J8.8Hz)，3.88(3H，s)，3.85(3H，s)
N- (2-benzylbenzo [ d ] oxazol-5-yl) -2-phenylacetamide
LCMS RT ═ 6.22 min, MH+343.1；1H NMR(CDCl3)：7.70(1H，s)，7.42(1H，s)，7.30-7.15(12H，m)，4.14(2H，s)，3.63(2H，s)
2, 3-dichloro-N- (2- (2, 3-dichlorophenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 8.09 min, MH+450.9；1H NMR(DMSO)：10.84(1H，s)，8.32(1H，d，J1.7Hz)，8.14(1H，dd，J8.91.5Hz)，7.95(1H，dd，J8.11.6Hz)，7.85(1H，d，J8.8Hz)，7.81(1H，dd，J8.01.6Hz)，7.73(1H，dd，J8.82.1Hz)，7.65-7.50(3H，m)
Method 1A (Compound Id)
2 '- (4-propylphenyl) -2, 6' -dibenzo [ d ] oxazole-6-carboxylic acid
1H NMR(DMSO)：13.20(1H，br)，8.58(1H，dd，J1.50.4Hz)，8.33-8.30(2H，m)，8.19(2H，d，J8.2Hz)，8.06-.802(2H，m)，7.93(1H，d，J8.3Hz)，7.50(2H，d，J8.4Hz)，2.69(2H，t，J7.8Hz)，1.73-1.61(2H，m)，0.94(3H，t，J7.4Hz)
Method 1A (Compound Ie)
4-amino-N- (4- (5-bromobenzo [ d ] oxazol-2-yl) phenyl) benzamide
LCMS RT ═ 6.87 min, MH+408.0；1H NMR(DMSO)：10.14(1H，s)，8.16(2H，d，J8.9Hz)，8.07-8.01(3H，m)，7.79-7.74(3H，m)，7.57(1H，dd，J8.62.0Hz)，6.62(2H，d，J8.7Hz)，5.86(2H，s)
Method 1B (Compound I)
2-benzyl-5-nitrobenzo [ d ] oxazoles
2-Phenylacetyl chloride (290. mu.L, 2.15mmol) was added to 2-amino-4-nitrophenol (300mg, 1.95mmol) in dioxane (2.5mL) at room temperature. The reaction vessel was heated in a microwave at 210 ℃ for 15 minutes. After cooling, the mixture was slowly poured into 1M aqueous sodium hydroxide (50ml), and the resulting precipitate was filtered and washed with water. The resulting solid was purified by column chromatography using a gradient (ethyl acetate/hexane 1:7v/v to ethyl acetate/hexane 1: 5v/v)) to give 165mg (33%) of the title compound. (LCMS RT ═ 6.47 minutes, MH+255.2)1H NMR(DMSO)：8.60(1H，d，J2.4Hz)，8.30(1H，dd，J9.02.4Hz)，7.95(1H，d，J9.0Hz)，7.43-7.27(5H，m)，4.44(2H，s)
All compounds described below were prepared using the same general procedure. The acid chlorides used are either commercially available or synthesized from the corresponding carboxylic acids using standard conditions.
2- (benzo [ d ] [ l, 3] dioxol-5-yl) -5-nitrobenz [ d ] oxazole
LCMS RT ═ 6.74 min, MH+284.9；1H NMR(DMSO)：8.60(1H，d，J2.3Hz)，8.31(1H，dd，J8.92.3Hz)，7.99(1H，d，J9.0Hz)，7.82(1H，dd，J8.21.7Hz)，7.66(1H，d，J1.6Hz)，7.18(1H，d，J8.4Hz)，6.20(2H，s)
2- (4-chlorophenyl) -5, 6-methylenedioxybenzoxazole
LCMS RT 7.54 min MH+274.0；1H NMR(DMSO)：8.11(2H，d，J8.8Hz)，7.66(2H，d，J8.7Hz)，7.49(1H，s)，7.36(1H，s)，6.13(2H，s)
5-tert-butyl-2- (4-chlorophenyl) benzo [ d ] oxazole
LCMS RT ═ 10.20 min, MH+286.0；1H NMR(DMSO)：8.20(2H，d，J8.6Hz)，7.80(1H，d，J1.9Hz)，7.72-7.68(3H，m)，7.52(1H，dd，J8.72.0Hz)，1.37(9H，s)
2- (3, 4-dichlorophenyl) -6-nitrobenzo [ d ] oxazole
LCMS RT 8.40 min;1H NMR(DMSO)：8.77(1H，d，J2.1Hz)，8.40(1H，d，J2.0Hz)，8.36(1H，dd，J8.82.2Hz)，8.21(1H，dd，J8.52.1Hz)，8.07(1H，d，J8.8Hz)，7.96(1H，d，J8.4Hz)
2- (4-chlorophenyl) benzo [ d ] oxazole-5-sulfonamide
LCMS RT ═ 6.04 min;1H NMR(DMSO)：8.27-8.22(3H，m)，8.02(1H，d，J8.6Hz)，7.95-7.91(1H，m)，7.74-7.71(2H，m)，7.50(2H，s)
5-chloro-2- (4-chlorophenyl) -6-nitrobenzo [ d ] oxazole
LCMS RT 8.10 min;1H NMR(DMSO)：8.73(1H，s)，8.31(1H，s)，8.24(2H，d，J8.7Hz)，7.76(2H，d，J8.7Hz)
5-nitro-2- (4- (trifluoromethoxy) phenyl) benzo [ d ] oxazole
LCMS RT 7.66 min;1H NMR(DMSO)：8.72(1H，d，J2.3Hz)，8.38(3H，m)，8.09(1H，d，J8.8Hz)，7.66(2H，d，J8.2Hz)
2- (3, 4-dichlorophenyl) benzo [ d ] oxazole [ l, 3] dioxole
LCMS RT 8.70 min MH+307.9；1H NMR(CDCl3)：8.18(1H，d，J2.0Hz)，7.91(1H，dd，J8.42.0Hz)，7.50(1H，d，J8.4Hz)，7.09(1H，s)，6.99(1H，s)，5.99(2H，s)
2- (furan-2-yl) -5-nitrobenzo [ d ] oxazoles
LCMS RT 6.24 min;1H NMR(DMSO)：8.66(1H，d，J2.3Hz)，8.35(1H，dd，J9.02.4Hz)，8.18(1H，d，J1.0Hz)，8.05(1H，d，J9.0Hz)，7.62(1H，d，J3.5Hz)，6.90-6.88(1H，m)
2- (benzo [ d ] [1, 3] dioxol-5-yl) -5-chloro-6-nitrobenzo [ d ] oxazole
LCMS RT 7.21 min;1H NMR(DMSO)：8.68(1H，s)，8.23(1H，s)，7.83(1H，dd，J8.21.6Hz)，7.66(1H，d，J1.7Hz)，7.20(1H，d，J8.4Hz)，6.22(2H，s)
5- (ethylsulfonyl) -2- (yl-2-yl) benzo [ d ] oxazole
LCMS RT ═ 6.94 min, MH+338.1；1H NMR(DMSO)：8.90(1H，br)，8.34(1H，d，J1.4Hz)，8.30(1H，dd，J8.61.7Hz)，8.24-8.05(4H，m)，7.99(1H，dd，J8.51.8Hz)，7.73-7.64(2H，m)，3.41(2H，q，J7.3Hz)，1.15(3H，t，J7.3Hz)
2- (3-chloro-2-fluorophenyl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 6.48 min MH+338.8；1H NMR(DMSO)：8.40(1H，dd，J1.70.5Hz)，8.27-8.21(1H，m)，8.14(1H，dd，J8.60.4Hz)，8.01(1H，dd，J8.61.8Hz)，7.97-7.92(1H，m)，7.51(1H，td，J8.01.0Hz)，3.41(2H，q，J7.3Hz)，1.13(3H，t，J7.3Hz)
2-cyclohexyl-5- (ethylsulfonyl) benzo [ d ] oxazoles
LCMS RT ═ 6.57 min, MH+293.9；1H NMR(DMSO)：8.20(1H，d，J1.5Hz)，7.97(1H，dd，J8.5Hz)，7.88(1H，dd，J8.61.8Hz)，3.35(2H，q，J7.4Hz)，3.13-3.04(1H，m)，2.14-2.09(2H，m)，1.82-1.58(5H，m)，1.50-1.18(3H，m)，1.10(3H，t，J7.4Hz)
2- (5-Chloropyridin-2-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 5.92 min MH+323.1；1H NMR(DMSO)：8.91(1H，d，J2.4Hz)，8.42-8.39(2H，m)，8.25(1H，dd，J8.52.4Hz)，8.16(1H，d，J8.6Hz)，8.03(1H，dd，J8.61.8Hz)，3.41(2H，q，J7.2Hz)，1.13(3H，t，J7.3Hz)
2- (benzo [ d ] [ l, 3] dioxol-5-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT ═ 6.09 minutes, MH+332.0；1H NMR(DMSO)：8.26(1H，dd，J1.80.5Hz)，8.03(1H，dd，J8.50.5Hz)，7.92(1H，dd，J8.51.8Hz)，7.83(1H，dd，J8.21.7Hz)，7.68(1H，d，J1.6Hz)，7.19(1H，d，J8.2Hz)，6.20(2H，s)，3.39(2H，q，J7.3Hz)，1.12(3H，t，J7.3Hz)
5-chloro-2- (4- (methylsulfonyl) phenyl) benzo [ d ] oxazole
LCMS RT 6.43 min;1H NMR(DMSO)：8.45(2H，d，J8.4Hz)，8.18(2H，d，J8.5Hz)，8.02(1H，d，J1.9Hz)，7.92(1H，d，J8.7Hz)，7.56(1H，dd，J8.72.1Hz)
2- (2, 2-difluorobenzo [ d ] [ l, 3] dioxol-5-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT 6.70 min;1H NMR(DMSO)：8.32(1H，dd，J1.80.5Hz)，8.24(1H，d，J1.6Hz)，8.16(1H，dd，J8.51.7Hz)，8.09(1H，dd，J8.60.5Hz)，7.97(1H，dd，J8.51.8Hz)，7.71(1H，d，J8.5Hz)，3.40(2H，q，J7.3Hz)，1.13(3H，t，J7.4Hz)
2- (4-chlorophenyl) benzo [ d ] oxazolyl-6-ol
LCMS RT ═ 6.42 min, MH+246.0；1H NMR(DMSO)：9.94(1H，s)，8.13(2H，d，J8.6Hz)，7.66(2H，d，J8.6Hz)，7.60(1H，d，J8.6Hz)，7.10(1H，d，J2.2Hz)，6.87(1H，dd，J8.72.3Hz)
2- (5- (ethylsulfonyl) benzo [ d ] oxazol-2-yl) naphthalen-1-ol
LCMS RT 7.77 min, MH+353.9；1H NMR(DMSO)：12.24(1H，s)，8.44-8.39(2H，m)，8.19-7.98(4H，m)，7.77-7.63(3H，m)，3.42(2H，q，J7.3Hz)，1.15(3H，t，J7.3Hz)
2- (benzofuran-5-yl) -5- (ethylsulfonyl) benzo [ d ] oxazole
LCMS RT ═ 6.47 min, MH+328.2；1H NMR(DMSO)：8.61(1H，d，J1.7Hz)，8.31(1H，d，J1.7Hz)，8.22(1H，dd，J8.51.7Hz)，8.19(1H，d，J2.2Hz)，8.09(1H，d，J8.5Hz)，7.95(1H，dd，J8.51.9Hz)，7.88(1H，d，J8.7Hz)，7.19-7.17(1H，m)，3.40(2H，q，J7.4Hz)，1.15(3H，t，J7.3Hz)
2- (4-chlorophenyl) -N, N-diethylbenzo [ d ] oxazole-5-sulfonamide
LCMS RT 7.75 min MH+364.9；1H NMR(DMSO)：8.26-8.21(3H，m)，8.03(1H，d，J8.6Hz)，7.89(1H，dd，J8.61.8Hz)，7.74(2H，d，J8.6Hz)，3.22(4H，q，J7.2Hz)，1.06(6H，t，J7.2Hz)
2- (Yl-2-Yl) -5- (trifluoromethoxy) benzo [ d ] oxazole
LCMS RT ═ 9.10 min, MH+330.1；1H NMR(DMSO)：8.88(1H，br)，8.27(1H，dd，J8.51.7Hz)，8.23-8.19(1H，m)，8.16(1H，d，J8.7Hz)，8.08-8.04(1H，m)，7.97(1H，d，J8.9Hz)，7.95-7.93(1H，m)，7.73-7.64(2H，m)，7.52-7.47(1H，m)
2- (naphthalen-2-yl) benzo [ d ] oxazole-5-carboxylic acid
LCMS RT 4.83 min, MH+289.0；1H NMR(DMSO)：13.20(1H，br)，8.89(1H，br)，8.36(1H，dd，J1.60.5Hz)，8.30(1H，dd，J8.61.8Hz)，8.24-8.20(1H，m)，8.17(1H，d，J8.8Hz)，8.10-8.04(2H，m)，7.94(1H，dd，J8.50.5Hz)，7.73-7.63(2H，m)
2- (Yl-2-Yl) benzo [ d ] oxazoles
LCMS RT 8.19 min, MH+246.1；1H NMR(DMSO)：8.86(1H，br)，8.29(1H，dd，J8.61.8Hz)，8.22-8.18(1H，m)，8.15(1H，d，J8.7Hz)，8.07-8.03(1H，m)，7.88-7.83(2H，m)，7.71-7.62(2H，m)，7.51-7.42(2H，m)
5-tert-butyl-2- (yl-2-yl) benzo [ d ] oxazole
LCMS RT ═ 10.50 min, MH+302.2；1H NMR(CDCl3)：8.70(1H，s)，8.25(1H，dd，J8.61.5Hz)，7.94-7.89(2H，m)，7.85-7.81(1H，m)，7.77(1H，d，J1.6Hz)，7.54-7.45(3H，m)，7.37(1H，dd，J8.51.8Hz)，1.35(9H，s)
5, 6-difluoro-2- (naphthalen-2-yl) benzo [ d ] oxazoles
LCMS RT 8.57 min MH+282.1；1H NMR(DMSO)：8.82(1H，br)，8.24(1H，dd，J8.61.8Hz)，8.21-8.12(3H，m)，8.07-8.00(2H，m)，7.72-7.63(2H，m)
1- (2 '- (3', 4 '-dichlorophenyl) benzo [ d ] oxazol-5' -yl) ethaneketone
LCMS RT 8.19 min, MH+305.9；1H NMR(DMSO)：8.45(1H，dd，J1.70.5Hz)，8.38(1H，d，J2.0Hz)，8.18(1H，dd，J8.52.1Hz)，8.09(1H，dd，J8.61.8Hz)，7.96-7.91(2H，m)，2.69(3H，s)
2- (4-chlorophenyl) -6-methylbenzo [ d ] oxazole
LCMS RT 8.41 min MH+244.1；1H NMR(DMSO)：8.18(2H，d，J8.7Hz)，7.72-7.61(4H，m)，7.27-7.23(1H，m)，2.48(3H，s)
5-methyl-2- (yl-2-yl) benzo [ d ] oxazole
LCMS RT 8.82 min, MH+260.2；1H NMR(DMSO)：8.83(1H，d，J1.1Hz)，8.26(1H，dd，J8.61.7Hz)，8.21-8.16(1H，m)，8.13(1H，d，J8.7Hz)，8.06-8.02(1H，m)，7.72-7.64(4H，m)，7.30-7.26(1H，m)，2.47(3H，s)
Method 1C (Compound I)
6-nitro-2-phenyl-oxazolo [5, 4-b ] pyridine
N- (5-Nitro-2-oxo-1, 2-dihydropyridin-3-yl) benzamide (300mg, 1.16mmol) was added to polyphosphoric acid at 165 ℃. The resulting mixture was then heated to 165 ℃ for 30 minutes. The solution was then poured into water. The resulting precipitate was collected by filtration, dissolved in diethyl ether, filtered through alumina and evaporated to give 9mg (3%) of the title compound.
1H NMR(DMSO)：9.31(1H，d，J2.5Hz)，9.12(1H，d，J2.5Hz)，8.32-8.27(2H，m)，7.79-7.67(3H，m)
All compounds described below were prepared using the same general procedure.
5-nitro-2- (pyridin-2-yl) benzo [ d ] oxazoles
LCMS RT 5.83 min MH+241.9；1H NMR(DMSO)：8.87-8.84(1H，m)，8.78(1H，d，J2.3Hz)，8.44-8.40(2H，m)，8.16-8.10(2H，m)，7.74-7.69(1H，m)
6-nitro-2- (pyridin-2-yl) benzo [ d ] oxazoles
LCMS RT 5.84 min MH+242.0；1H NMR(DMSO)：8.79-8.76(2H，m)，8.34(1H，dt，J7.91.0Hz)，8.29(1H，dd，J8.82.0Hz)，8.07-8.02(2H，m)，7.64(1H，ddd，J7.74.81.2Hz)
2- (5-butylpyridin-2-yl) -5-nitrobenzo [ d ] oxazoles
LCMS RT 7.32 min MH+298.1；1H NMR(DMSO)：8.68(1H，dd，J2.30.3Hz)，8.64(1H，dd，J2.10.5Hz)，8.33(1H，dd，J9.02.4Hz)，8.26(1H，dd，J8.00.6Hz)，8.05(1H，dd，J9.00.3Hz)，7.88(1H，dd，J8.12.1Hz)，2.70-2.66(2H，m)，1.62-1.52(2H，m)，1.34-1.22(2H，m)，0.86(3H，t，J7.4Hz)
Method 1D (Compound I)
2- (2, 4-difluorophenyl) -5, 6-dimethylbenzo [ d ] oxazole
A suspension of 2- (2, 4-difluorobenzamide) -4, 5-dimethylphenyl-2, 4-difluorobenzoate (90mg, 0.22mmol) and 4-methylbenzenesulfonic acid (82mg, 0.43mmol) in xylene (2mL) was heated to reflux for 16 hours. The solution was cooled, diluted with ethyl acetate, washed with aqueous sodium bicarbonate, and then brine. The combined organic layers were dried over anhydrous magnesium sulfate and evaporated. Using ethyl acetate/hexane 1: the resulting solid was purified by column chromatography elution at 15v/v to yield 36mg (64%) of the title compound (LCMS RT ═ 7.81 min, MH)+260.0)。
1H NMR(DMSO)：8.30-8.22(1H，m)，7.63-7.52(3H，m)，7.39-7.30(1H，m)，2.37(3H，s)，2.35(3H，s)
Method 2A (Compound Ib)
2-p-tolylbenzo [ d ] oxazol-5-amine
Palladium on charcoal (480mg) was added to 5-nitro-2-p-tolylbenzo [ d ] in ethyl acetate/acetic acid (250mL/1mL)]Oxazole (4.8g, 18.90 mmol). The reaction vessel was purged three times with nitrogen, then three times with hydrogen, and then stirred under a hydrogen atmosphere for 16 hours. In thatBefore filtration on a pad, the mixture was washed with ethyl acetateA pad. Organic solutionWith saturated Na2CO3Washed with aqueous solution, followed by brine. The combined organic layers were over anhydrous MgSO4Drying and evaporation gave 2.5g (60%) of the title compound.
1H NMR(DMSO)：8.02(2H，d，J8.2Hz)，7.39(3H，d，J8.5Hz)，6.86(1H，d，J2.0Hz)，6.65(1H，dd，J8.72.2Hz)，5.09(2H，s)，2.40(3H，s)
Method 2B (Compound Ib)
As in method 2A, except that ethyl acetate/acetic acid was replaced with ethanol. After evaporation of the solvent, the material was taken up in 2M HCl, the resulting precipitate was removed, and the solution was basified with 2N NaOH to give the title compound as a precipitate.
2-phenylbenzo [ d ] oxazol-6-amines
LCMS RT 5.93 min MH+211.1；1H NMR(DMSO)：8.10-8.07(2H，m)，7.58-7.54(3H，m)，7.42(1H，d，J8.4Hz)，6.83(1H，d，J1.9Hz)，6.65(1H，dd，J8.52.0Hz)，5.46(2H，s)
Method 2C (Compound Ib)
2- (4- (trifluoromethoxy) phenyl) benzo [ d ] oxazol-5-amine
Ammonium formate (827mg, 13.1mmol) and palladium on charcoal (85mg) were added to 5-nitro-2- (4- (trifluoromethoxy) phenyl) benzo [ d ] in ethanol (20mL)]Oxazole (850mg, 2.62 mmol). The mixture was stirred at room temperature for 20 minutes and then washed withThe pad was filtered and washed with ethyl acetate. The organic solution was washed with water, followed by brine. Over anhydrous MgSO4The combined organic layers were dried and evaporated to give 434mg (56%) of the title compound (LCMS RT ═ 6.51 min, MH)+294.9)。
1H NMR(DMSO)：8.25(2H，d，J8.9Hz)，7.62-7.56(2H，m)，7.44(1H，d，J8.7Hz)，6.89(1H，d，J2.0Hz)，6.70(1H，dd，J8.72.3Hz)，5.16(2H，s)
Method 2D (Compound Ib)
2-p-tolylbenzo [ d ] oxazolyl-4-amine
Tin (II) chloride (1.23g, 6.5mmol) was added to 4-nitro-2-p-tolylbenzo [ d ] in ethanol (20mL)]Oxazole (330mg, 1.30 mmol). The suspension was stirred at 70 ℃ for 16 hours. After cooling, the solution was poured onto ice/water and saturated NaHCO3Neutralizing with water solution. The aqueous layer was then extracted 2 times with ethyl acetate (500 mL). Over anhydrous MgSO4The combined organic layers were dried and evaporated to yield 188mg (65%) of the title compound (LCMS RT ═ 6.76 min, MH)+225.1)。
1H NMR(DMSO)：8.04(2H，d，J8.2Hz)，7.41(2H，d，J8.0Hz)，7.07(1H，t，J8.0Hz)，6.85(1H，dd，J8.00.8Hz)，6.55(1H，dd，J8.00.8Hz)，5.67(2H，s)，2.41(3H，s)
The following compounds were prepared using the same general procedure.
2-phenyl-oxazolo [5, 4-b ] pyridyl-6-amines
LCMS RT 5.41 min MH+212.1；1H NMR(DMSO)：8.19-8.15(2H，m)，7.73(1H，d，J2.4Hz)，7.63-7.58(3H，m)，7.32(1H，d，J2.4Hz)，5.38(2H，s)
Method 2E (Compound Ib)
2-p-tolylbenzo [ d ] oxazolyl-6-amine
Iron powder (2.14g, 38.3mmol) and ammonium chloride (819mg, 15.3mmol) were added to ethanol at 70 ℃: water 2: 6-nitro-2-p-tolylbenzo [ d ] in 1v/v (60mL)]Oxazole (2.1g, 8.27 mmol). The suspension was stirred at reflux for 16 hours. After cooling, then useThe pad filters the solution and is washed with ethanol. After evaporation of the solvent, the aqueous layer was extracted with ethyl acetateTwice for each time. Over anhydrous MgSO4The combined organic layers were dried and evaporated. The resulting solid was purified by column chromatography (eluting with ethyl acetate: hexane ═ 1:3 v/v) to give 70mg (4%) of the title compound (LCMS RT ═ 6.12 min, MH)+223.1)。
1H NMR(DMSO)：7.97(2H，d，J8.1Hz)，7.40-7.36(3H，m)，6.82(1H，d，J1.9Hz)，6.64(1H，dd，J8.52.0Hz)，5.41(2H，s)，2.39(3H，s)
The following compounds were prepared by the same method.
2-phenethylbenzo [ d ] oxazol-5-amines
LCMS RT 5.82 min MH+238.9；1H NMR(DMSO)：7.29-7.16(6H，m)，6.76(1H，d，J1.9Hz)，6.57(1H，dd，J8.62.2Hz)，4.98(2H，s)，3.19-3.06(4H，m)
2- (benzo [ d ] [ l, 3] dioxol-5-yl) benzo [ d ] oxazol-5-amine
LCMS RT 5.77 min MH+254.9；1H NMR(DMSO)：7.69(1H，dd，J8.21.7Hz)，7.58(1H，d，J1.7Hz)，7.37(1H，d，J8.6Hz)，7.11(1H，d，J8.2Hz)，6.84(1H，d，J2.0Hz)，6.64(1H，dd，J8.82.2Hz)，6.16(2H，s)，5.07(2H，s)
2- (benzo [ d ] [ l, 3] dioxol-5-yl) -5-chlorobenzo [ d ] oxazolyl-6-amine
LCMS RT ═ 6.52 min, MH+289.1；1H NMR(DMSO)：7.72(1H，dd，J8.21.8Hz)，7.69(1H，s)，7.61(1H，d，J1.6Hz)，7.17(1H，d，J8.2Hz)，7.13(1H，s)，6.21(2H，s)，5.66(2H，s)
Method 2F (Compound Ib)
As method 2E, except that THF, water (2:1v/v) was used instead of ethanol, water (2:1 v/v).
2- (3, 4-dichlorophenyl) benzo [ d ] oxazolyl-6-amine
LCMS RT 7.12 min, MH + 278.1;1H NMR(DMSO)：8.22(1H，d，J1.8Hz)，8.03(1H，dd，J8.42.0Hz)，7.83(1H，d，J8.4Hz)，7.44(1H，d，J8.4Hz)，6.82(1H，d，J2.0Hz)，6.68(1H，dd，J8.62.0Hz)，5.57(2H，s)
method 3A (Compound II)
3-phenyl-N- (2-phenylbenzo [ d ] oxazol-5-yl) propanamide
3-Phenylpropionyl chloride (44.1mg, 0.26mmol) was added to 2-phenylbenzo [ d ] at room temperature]To a solution of oxazol-5-amine (50mg, 0.24mmol) in dichloromethane (2mL) was added diisopropylethylamine (82 μ L, 0.48mmol) immediately. The resulting mixture was stirred at room temperature for 16 hours. Dichloromethane was added and the organic layer was washed with Na2CO3Is washed with a saturated aqueous solution. Over anhydrous MgSO4The combined organic layers were dried and evaporated. The resulting solid was dissolved in methanol and passed through an acidic clean column (fromThe resulting silica quaternary ammonium SPE-AX) was evaporated to give 61.1mg (75%) of the title compound (LCMS RT ═ 6.45 min, MH)+343.2)。
1H NMR(DMSO)：10.11(1H，s)，8.22-8.15(3H，m)，7.71(1H，d，J8.8Hz)，7.66-7.59(3H，m)，7.51(1H，dd，J8.92.1Hz)，7.33-7.17(5H，m)，2.96(2H，t，J7.2Hz)，2.67(2H，t，J7.I Hz)
The following compounds were prepared using the same general procedure.
N- (2-phenylbenzo [ d ] oxazol-5-yl) acetamide
LCMS RT 5.16 min MH+253.1；1H NMR(DMSO)：10.14(1H，s)，8.21-8.14(3H，m)，7.71(1H，d，J8.8Hz)，7.65-7.60(3H，m)，7.51(1H，dd，J9.02.1Hz)，2.09(3H，s)
N- (2-phenylbenzo [ d ] oxazol-5-yl) propanamide
LCMS RT5.49 min, MH+267.1；1H NMR(DMSO)：10.09(1H，s)，8.21-8.16(3H，m)，7.71(1H，d，J8.8Hz)，7.66-7.61(3H，m)，7.54(1H，dd，J9.02.1Hz)，2.37(2H，q，J7.6Hz)，1.12(3H，t，J7.6Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) butanamide
LCMS RT 5.78 min, MH+281.1；1H NMR(DMSO)：10.09(1H，s)，8.21-8.16(3H，m)，7.71(1H，d，J8.8Hz)，7.64-7.60(3H，m)，7.54(1H，dd，J9.02.1Hz)，2.33(2H，q，J7.6Hz)，1.69-1.61(2H，m)，0.94(3H，t，J7.6Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) pentanamide
LCMS RT ═ 6.21 min, MH+295.1；1H NMR(DMSO)：10.09(1H，s)，8.21-8.16(3H，m)，7.71(1H，d，J8.8Hz)，7.65-7.60(3H，m)，7.54(1H，dd，J9.02.1Hz)，2.35(2H，q，J7.6Hz)，1.66-1.58(2H，m)，1.39-1.31(2H，m)，0.92(3H，t，J7.6Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.79 min MH+281.1；1H NMR(DMSO)：10.02(1H，s)，8.22-8.18(3H，m)，7.71(1H，d，J8.8Hz)，7.66-7.60(3H，m)，7.55(1H，dd，J9.02.1Hz)，2.67-2.58(1H，m)，1.14(6H，s)
N- (2-phenylbenzo [ d ] oxazol-5-yl) furan-2-carboxamide
LCMS RT 5.82 min MH+305.1；1H NMR(DMSO)：10.42(1H，s)，8.26-8.20(3H，m)，7.97(1H，dd，J1.70.8Hz)，7.77(2H，d，J1.3Hz)，7.66-7.62(3H，m)，7.38(1H，d，J3.4Hz)，6.73(1H，dd，J3.41.7Hz)
4-chloro-N- (2-p-tolylbenzo [ d ] oxazol-5-yl) benzamide
LCMS RT 7.23 min MH+363.1；1H NMR(DMSO)：10.55(1H，s)，8.32-8.31(1H，m)，8.17(2H，d，J8.1Hz)，8.08(2H，d，J8.6Hz)，7.84-7.77(2H，m)，7.70(2H，d，J8.6Hz)，7.50(2H，d，J8.1Hz)，2.49(3H，s)
4-methoxy-N- (2-p-tolylbenzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 6.41 min, MH+359.1；1H NMR(DMSO)：10.35(1H，s)，8.33(1H，s)，8.17(2H，d，J8.1Hz)，8.07(2H，d，J8.7Hz)，7.81(2H，s)，7.51(2H，d，J8.3Hz)，7.16(2H，d，J8.8Hz)，3.17(3H，s)，2.49(3H，s)
Method 3B (Compound II)
As in method 3A except that triethylamine was used as the base instead of diisopropylamine.
N- (2-phenylbenzo [ d ] oxazol-5-yl) nicotinamide
LCMS RT 5.48 min MH+316.1；1H NMR(DMSO)：10.70(1H，s)，9.21(1H，d，J2.1Hz)，8.85(1H，dd，J4.81.6Hz)，8.40(1H，dt，J8.02.0Hz)，8.37(1H，d，J1.8Hz)，8.30-8.27(2H，m)，7.89-7.80(2H，m)，7.72-7.64(4H，m)
N- (2-phenylbenzo [ d ] oxazol-5-yl) isonicotinamide
LCMS RT 5.46 min MH+316.1；1H NMR(DMSO)：10.76(1H，s)，8.88(2H，d，J5.9Hz)，8.36(1H，d，J1.7Hz)，8.31-8.27(2H，m)，7.97(2H，d，J6.1Hz)，7.90-7.80(2H，m)，7.73-7.68(3H，m)
4-chloro-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamides
LCMS RT 7.07 min, MH+349.1；1H NMR(DMSO)：10.57(1H，s)，8.35-8.34(1H，m)，8.30-8.27(2H，m)，8.09(2H，d，J8.6Hz)，7.88-7.80(2H，m)，7.72-7.67(5H，m)
4-methyl-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamides
LCMS RT ═ 6.80 min, MH+329.2；1H NMR(DMSO)：10.41(1H，s)，8.37-8.35(1H，m)，8.30-8.26(2H，m)，7.98(2H，d，J8.1Hz)，7.84(2H，s)，7.72-7.67(3H，m)，7.43(2H，d，J8.0Hz)，2.47(3H，s)
4-methoxy-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamides
LCMS RT ═ 6.37 minutes, MH+345.1；1H NMR(DMSO)：10.33(1H，s)，8.35(1H，s)，8.30-8.26(2H，m)，8.06(2H，d，J8.7Hz)，7.83(2H，s)，7.71-7.67(3H，m)，7.14(2H，d，J8.8Hz)，3.92(3H，s)
2-methoxy-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamides
LCMS RT 7.06 min MH+345.1；1H NMR(DMSO)：10.37(1H，s)，8.38-8.36(1H，m)，8.30-8.26(2H，m)，7.84-7.56(7H，m)，7.27(1H，d，J8.4Hz)，7.14(1H，t，J7.3Hz)，3.99(3H，s)
4- (dimethylamino) -N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 6.63 min, MH+358.2；1H NMR(DMSO)：10.10(1H，s)，8.35-8.34(1H，m)，8.30-8.26(2H，m)，7.96(2H，d，J8.9Hz)，7.82-7.80(2H，m)，7.71-7.68(3H，m)，6.84(2H，d，J8.9Hz)，3.08(6H，s)
3, 4-dichloro-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamide
LCMS RT 7.95 min MH+382.8；1H NMR(DMSO)：10.63(1H，s)，8.37-8.26(4H，m)，8.04(1H，dd，J8.42.1Hz)，7.92-7.78(3H，m)，7.73-7.65(3H，m)
N- (2-phenylbenzo [ d ] oxazol-5-yl) -4- (trifluoromethyl) benzamide
LCMS RT 7.19 min, MH+383.1；1H NMR(DMSO)：10.72(1H，s)，8.37-8.24(5H，m)，8.00(2H，d，J8.4Hz)，7.89-7.82(2H，m)，7.74-7.67(3H，m)
3, 5-dichloro-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 8.30 min, MH+382.9；1H NMR(DMSO)：10.67(1H，s)，8.33-8.26(3H，m)，8.09(2H，d，J2.1Hz)，7.96(1H，t，J2.0Hz)，7.89-7.78(2H，m)，7.72-7.67(3H，m)
4-fluoro-N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamides
LCMS RT ═ 6.53 min, MH+333.2；1H NMR(DMSO)：10.50(1H，s)，8.34-8.33(1H，m)，8.39-8.26(2H，m)，8.16-8.11(2H，m)，7.86-7.79(2H，m)，7.71-7.65(3H，m)，7.45(2H，t，J8.8Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) biphenyl-4-carboxamide
LCMS RT 7.74 min MH+391.1；1H NMR(DMSO)：10.55(1H，s)，8.39-8.38(1H，m)，8.31-8.27(2H，m)，8.17(2H，d，J8.5Hz)，7.93(2H，d，J8.4Hz)，7.86-7.83(4H，m)，1.12-1.69(3H，m)，7.62-7.50(3H，m)
2-phenyl-N- (2-phenylbenzo [ d ] oxazol-5-yl) acetamide
LCMS RT ═ 6.32 min, MH+329.2；1H NMR(DMSO)：10.42(1H，s)，8.27-8.21(3H，m)，7.78(1H，d，J8.9Hz)，7.71-7.65(3H，m)，7.61(1H，dd，J8.92.1Hz)，7.45-7.30(5H，m)，3.75(2H，s)
N- (2-phenylbenzo [ d ] oxazol-5-yl) cinnamamides
LCMS RT 6.86 min, MH+341.1；1H NMR(DMSO)：10.48(1H，s)，8.37(1H，d，J1.9Hz)，8.29-8.26(2H，m)，7.83(1H，d，J8.9Hz)，7.73-7.67(7H，m)，7.56-7.48(3H，m)，6.93(1H，d，J15.6Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) -1-naphthamides
LCMS RT 7.07 min, MH+365.0；1H NMR(DMSO)：10.82(1H，s)，8.44(1H，s)，8.31-8.28(3H，m)，8.18-8.10(2H，m)，7.88-7.83(3H，m)，7.73-7.65(6H，m)
N- (2-phenylbenzo [ d ] oxazol-5-yl) -2-naphthamides
LCMS RT 7.37 min MH+365.1；1H NMR(DMSO)：10.69(1H，s)，8.69(1H，s)，8.42(1H，s)，8.31-8.28(2H，m)，8.20-8.08(4H，m)，7.90-7.88(2H，m)，7.75-7.68(5H，m)
N- (2-phenylbenzo [ d ] oxazol-5-yl) thiophene-2-carboxamide
LCMS RT ═ 6.31 minutes, MH+321.1；1H NMR(DMSO)：10.47(1H，s)，8.30-8.26(3H，m)，8.12(1H，dd，J3.81.1Hz)，7.94(1H，dd，J5.01.1Hz)，7.85(1H，d，J8.8Hz)，7.77(1H，dd，J8.92.0Hz)，7.73-7.65(3H，m)，7.33-7.30(1H，m)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamides
LCMS RT 5.63 min MH+315.8；1H NMR(DMSO)：10.53(1H，s)，9.45-9.42(1H，m)，8.88(1H，dd，J4.91.6Hz)，8.62(1H，dt，J8.01.8Hz)，8.42-8.40(1H，m)，8.06(2H，dd，J6.61.2Hz)，7.88(2H，s)，7.75-7.59(4H，m)
4-chloro-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 6.12 min, MH+349.9；1H NMR(DMSO)：10.58(1H，s)，9.43-9.42(1H，m)，8.89-8.87(1H，m)，8.64-8.59(1H，m)，8.40-8.38(1H，m)，8.09(2H，d，J8.5Hz)，7.91-7.83(2H，m)，7.76-7.69(3H，m)
4-methyl-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 5.91 min MH+330.2；1H NMR(DMSO)：10.43(1H，s)，9.43(1H，dd，J2.10.9Hz)，8.88(1H，dd，J4.81.6Hz)，8.61(1H，dt，J8.01.9Hz)，8.40(1H，t，J1.2Hz)，7.98(2H，d，J8.2Hz)，7.87(2H，d，J1.2Hz)，7.75-7.70(1H，m)，7.43(2H，d，J8.0Hz)，2.47(3H，s)
4-methoxy-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 5.64 min MH+345.9；1H NMR(DMSO)：10.37(1H，s)，9.45(1H，dd，J1.60.8Hz)，8.90(1H，dd，J4.91.7Hz)，8.63(1H，dt，J8.01.9Hz)，8.41(1H，t，J1.2Hz)，8.08(2H，d，J8.5Hz)，7.88(2H，d，J1.2Hz)，7.77-7.72(1H，m)，7.17(2H，d，J8.7Hz)，3.94(3H，s)
2-methoxy-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 6.02 min, MH+345.9；1H NMR(DMSO)：10.33(1H，s)，9.38-9.36(1H，m)，8.82(1H，dd，J4.91.7Hz)，8.55(1H，dt，J8.01.8Hz)，8.36-8.34(1H，m)，7.82-7.73(2H，m)，7.69-7.65(2H，m)，7.57-7.50(1H，m)，7.21(1H，d，J8.4Hz)，7.09(1H，t，J7.6Hz)，3.93(3H，s)
4- (dimethylamino) -N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 5.82 min MH+358.9；1H NMR(DMSO)：10.13(1H，s)，9.45(1H，dd，J2.30.9Hz)，8.88(1H，dd，J4.81.6Hz)，8.64-8.59(1H，m)，8.40-8.39(1H，m)，7.97(2H，d，J9.1Hz)，7.86-7.85(2H，m)，7.75-7.70(1H，m)，6.86(2H，d，J9.1Hz)，3.08(6H，s)
3, 4-dichloro-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 6.78 min, MH+383.5；1H NMR(DMSO)：10.66(1H，s)，9.43(1H，d，J2.10.6Hz)，8.88(1H，dd，J4.81.6Hz)，8.61(1H，dt，J8.02.0Hz)，8.37(1H，d，J2.0Hz)，8.32(1H，d，J2.1Hz)，8.04(1H，dd，J8.42.1Hz)，7.92-7.82(3H，m)，7.75-7.71(1H，m)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) -4- (trifluoromethyl) benzamide
LCMS RT ═ 6.32 min, MH+383.6；1H NMR(DMSO)：10.68(1H，s)，9.37(1H，d，J2.1Hz)，8.82(1H，dd，J4.91.5Hz)，8.56(1H，dt，J8.02.0Hz)，8.34(1H，d，J1.7Hz)，8.20(2H，d，J8.1Hz)，7.95(2H，d，J8.4Hz)，7.88-7.79(2H，m)，7.69-7.65(1H，m)
3, 5-dichloro-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 7.06 min MH+383.7；1H NMR(DMSO)：10.69(1H，s)，9.43-9.41(1H，m)，8.88(1H，dd，J4.91.7Hz)，8.61(1H，dt，J8.02.0Hz)，8.37(1H，d，J1.9Hz)，8.09(2H，d，J1.9Hz)，7.96-7.82(3H，m)，7.75-7.71(1H，m)
4-fluoro-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 5.70 min MH+334.0；1H NMR(DMSO)：10.47(1H，s)，9.38-9.36(1H，m)，8.82(1H，dd，J4.91.7Hz)，8.56(1H，dt，J8.02.0Hz)，8.33-8.32(1H，m)，8.11-8.06(2H，m)，7.85-7.80(2H，m)，7.69-7.65(1H，m)，7.40(2H，t，J8.9Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) biphenyl-4-carboxamide
LCMS RT ═ 6.78 min, MH+391.6；
2-phenyl-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) acetamide
LCMS RT 5.63 min MH+329.7；1H NMR(DMSO)：10.46(1H，s)，9.41-9.39(1H，m)，8.87(1H，dd，J4.91.7Hz)，8.59(1H，dt，J8.02.0Hz)，8.26(1H，d，J2.0Hz)，7.82(1H，d，J8.8Hz)，7.73-7.69(1H，m)，7.64(1H，dd，J8.82.0Hz)，7.44-7.30(5H，m)，3.75(2H，s)
3-phenyl-N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT 5.84 min MH+343.8；1H NMR(DMSO)：10.14(1H，s)，9.35-9.34(1H，m)，8.81(1H，dd，J4.91.7Hz)，8.53(1H，dt，J8.02.0Hz)，8.19(1H，d，J2.0Hz)，7.76(1H，d，J8.8Hz)，7.69-7.63(1H，m)，7.54(1H，dd，J8.82.0Hz)，7.33-7.17(5H，m)，2.95(2H，t，J7.6Hz)，2.67(2H，t，J8.0Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) cinnamamide
LCMS RT ═ 6.03 min, MH+342.0；1H NMR(DMSO)：10.46(1H，s)，9.37-9.35(1H，m)，8.82(1H，dd，J4.91.7Hz)，8.55(1H，dt，J8.02.0Hz)，8.35(1H，d，J1.9Hz)，7.82(1H，d，J8.9Hz)，7.69-7.63(5H，m)，7.49-7.41(3H，m)，6.87(1H，d，J15.8Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT 4.97 min MH+267.9；1H NMR(DMSO)：10.08(1H，s)，9.34(1H，dd，J2.20.7Hz)，8.81(1H，dd，J4.91.7Hz)，8.53(1H，dt，J8.02.0Hz)，8.21(1H，d，J2.0Hz)，7.76(1H，d，J8.9Hz)，7.68-7.63(1H，m)，7.57(1H，dd，J9.02.1Hz)，2.37(2H，q，J7.6Hz)，1.12(3H，t，J7.6Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT 5.26 min MH+281.9；1H NMR(DMSO)：10.17(1H，s)，9.43(1H，dd，J2.20.7Hz)，8.89(1H，dd，J4.91.7Hz)，8.62(1H，dt，J8.02.0Hz)，8.29(1H，d，J2.0Hz)，7.84(1H，d，J8.9Hz)，7.76-7.72(1H，m)，7.65(1H，dd，J9.02.1Hz)，2.42(2H，q，J7.6Hz)，1.80-1.67(2H，m)，1.03(3H，t，J7.6Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) pentanamide
LCMS RT 5.60 min MH+296.0；1H NMR(DMSO)：10.09(1H，s)，9.36-9.33(1H，m)，8.81(1H，dd，J4.91.7Hz)，8.53(1H，dt，J8.02.0Hz)，8.20(1H，d，J2.0Hz)，7.75(1H，d，J8.9Hz)，7.648-7.64(1H，m)，7.57(1H，dd，J9.02.1Hz)，2.35(2H，q，J7.6Hz)，1.66-1.56(2H，m)，1.42-1.29(2H，m)，0.92(3H，t，J7.6Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.22 min MH+282.0；1H NMR(DMSO)：10.11(1H，s)，9.41(1H，dd，J2.20.7Hz)，8.87(1H，dd，J4.91.7Hz)，8.60(1H，dt，J8.02.0Hz)，8.29(1H，d，J2.0Hz)，7.83(1H，d，J8.9Hz)，7.74-7.69(1H，m)，7.65(1H，dd，J9.02.1Hz)，2.70(1H，t，J6.8Hz)，1.20(6H，d，J6.8Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) furan-2-carboxamide
LCMS RT 5.23 min MH+305.7；1H NMR(DMSO)：10.41(1H，s)，9.37(1H，dd，J2.20.8Hz)，8.82(1H，dd，J4.91.7Hz)，8.55(1H，dt，J8.02.0Hz)，8.30(1H，t，J1.3Hz)，7.97(1H，dd，J1.70.8Hz)，7.82-7.81(2H，m)，7.69-7.64(1H，m)，7.37(1H，dd，J3.50.8Hz)，6.74(1H，dd，J3.51.7Hz)
N- (2- (pyridin-3-yl) benzo [ d ] oxazol-5-yl) thiophene-2-carboxamide
LCMS RT 5.55 min MH+322.0；1H NMR(DMSO)：10.44(1H，s)，9.37(1H，dd，J2.20.8Hz)，8.82(1H，dd，J4.91.7Hz)，8.56(1H，dt，J8.02.0Hz)，8.28(1H，t，J1.3Hz)，8.06(1H，dd，J1.70.8Hz)，7.89(1H，dd，J5.01.0Hz)，7.83(1H，d，J9.0Hz)，7.77-7.73(1H，m)，7.70-7.65(1H，m)，7.26(1H，dd，J5.01.2Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) benzamides
LCMS RT ═ 6.82 min, MH+314.9；1H NMR(DMSO)：10.43(1H，s)，8.31-8.30(1H，m)，8.25-8.20(2H，m)，8.02-7.98(2H，m)，7.79(2H，d，J1.2Hz)，7.65-7.53(6H，m)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) nicotinamide
LCMS RT ═ 6.55 min, MH+386.8；1H NMR(DMSO)：10.57(1H，s)，9.14(1H，d，J2.1Hz)，8.78(1H，dd，J4.81.6Hz)，8.33(1H，dt，J8.02.0Hz)，8.14(1H，d，J1.8Hz)，7.96(2H，d，J9.0Hz)，7.70-7.52(3H，m)，6.82(2H，d，J9.1Hz)，3.50-3.41(4H，m)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) isonicotinamide
LCMS RT ═ 6.63 min, MH+386.8；1H NMR(DMSO)：10.69(1H，s)，8.87(2H，d，J6.1Hz)，8.20(1H，d，J1.5Hz)，8.04(2H，d，J9.1Hz)，7.96(2H，d，J6.0Hz)，7.77-7.69(2H，m)，6.89(2H，d，J9.1Hz)，3.50-3.46(4H，m)，1.21(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 7.84 min MH+386.1；1H NMR(DMSO)：10.43(1H，s)，8.22-8.20(1H，m)，8.06-8.01(4H，m)，7.72(2H，d，J1.2Hz)，7.68-7.58(3H，m)，6.89(2H，d，J9.1Hz)，3.51(4H，q，J7.0Hz)，1.21(6H，t，J7.0Hz)
4-chloro-N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 8.60 min MH+419.9；1H NMR(DMSO)：10.44(1H，s)，8.13(1H，s)，8.00-7.95(4H，m)，7.66-7.62(4H，m)，6.82(2H，d，J9.1Hz)，3.45(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -4-methylbenzamide
LCMS RT 8.28 min MH+400.2；1H NMR(DMSO)：10.28(1H，s)，8.14(1H，s)，7.97(2H，d，J8.9Hz)，8.03(2H，d，J8.1Hz)，7.65(2H，d，J1.2Hz)，7.36(2H，d，J8.1Hz)，6.82(2H，d，J9.1Hz)，3.44(4H，q，J7.0Hz)，2.40(3H，s)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -4-methoxybenzamide
LCMS RT 7.86 min MH+416.2；1H NMR(DMSO)：10.20(1H，s)，8.13-8.12(1H，m)，8.00-7.95(4H，m)，7.64(2H，d，J1.3Hz)，7.07(2H，d，J8.9Hz)，6.82(2H，d，J9.1Hz)，3.85(3H，s)，3.44(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -2-methoxybenzamide
LCMS RT 8.69 min MH+416.0；1H NMR(DMSO)：10.24(1H，s)，8.15(1H，d，J1.5Hz)，7.96(2H，d，J8.9Hz)，7.68-7.49(4H，m)，7.19(1H，d，J8.4Hz)，7.08(1H，t，J7.5Hz)，6.83(2H，d，J9.1Hz)，3.92(3H，s)，3.44(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -4- (dimethylamino) benzamide
LCMS RT 8.08 min MH+429.0；1H NMR(DMSO)：9.98(1H，s)，8.13(1H，s)，7.96(2H，d，J8.9Hz)，7.90(2H，d，J8.9Hz)，7.64-7.61(2H，m)，6.84-6.76(4H，m)，3.44(4H，q，J7.0Hz)，3.01(6H，s)，1.15(6H，t，J7.0Hz)
3, 4-dichloro-N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 9.66 min, MH+453.9；1H NMR(DMSO)：10.52(1H，s)，8.25(1H，d，J2.0Hz)，8.12(1H，d，J1.8Hz)，7.98-7.94(3H，m)，7.85(1H，d，J8.4Hz)，7.70-7.60(2H，m)，6.82(2H，d，J9.2Hz)，3.45(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -4- (trifluoromethyl) benzamide
LCMS RT 8.87 min MH+454.4；1HNMR(DMSO)：10.60(1H，s)，8.20-8.15(3H，m)，7.99-7.93(4H，m)，7.70-7.63(2H，m)，6.83(2H，d，J9.2Hz)，3.45(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
3, 5-dichloro-N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 10.25 min, MH+453.8；1H NMR(DMSO)：10.63(1H，s)，8.21-8.19(1H，m)，8.09(2H，d，J1.9Hz)，8.05(2H，d，J9.1Hz)，7.97(1H，t，J1.9Hz)，7.78-7.69(2H，m)，6.91(2H，d，J9.1Hz)，3.50(4H，q，J7.0Hz)，1.23(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -4-fluorobenzamide
LCMS RT 7.95 min MH+404.1；1H NMR(DMSO)：10.38(1H，s)，8.13-8.12(1H，m)，8.09-8.04(2H，m)，7.96(2H，d，J9.1Hz)，7.68-7.61(2H，m)，7.39(2H，t，J8.9Hz)，6.82(2H，d，J9.2Hz)，3.45(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) biphenyl-4-carboxamide
LCMS RT ═ 9.67 min, MH+461.9；1H NMR(DMSO)：10.42(1H，s)，8.18-8.17(1H，m)，8.09(2H，d，J8.5Hz)，7.98(2H，d，J9.0Hz)，7.87(2H，d，J8.6Hz)，7.78(2H，d，J7.1Hz)，7.71-7.65(2H，m)，7.45-7.41(3H，m)，6.82(2H，d，J9.2Hz)，3.45(4H，q，J7.0Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -2-phenylacetamide
LCMS RT 7.70 min MH+400.1；1H NMR(DMSO)：10.29(1H，s)，8.00(1H，d，J1.8Hz)，7.94(2H，d，J9.1Hz)，7.59(1H，d，J8.7Hz)，7.45-7.23(6H，m)，6.81(2H，d，J9.2Hz)，3.67(2H，s)，3.43(4H，q，J7.0Hz)，1.14(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) -3-phenylpropanamide
LCMS RT ═ 8.10 min, MH+413.9；1H NMR(DMSO)：10.03(1H，s)，7.99(1H，d，J1.9Hz)，7.94(2H，d，J9.1Hz)，7.58(1H，d，J8.7Hz)，7.40(1H，dd，J8.72.0Hz)，7.36-7.17(5H，m)，6.82(2H，d，J9.2Hz)，3.44(4H，q，J7.0Hz)，2.94(2H，d，J8.1Hz)，2.65(1H，d，J8.3Hz)，1.15(6H，t，J7.0Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT ═ 6.79 min, MH+338.2；1H NMR(DMSO)：10.11(1H，s)，8.07(1H，d，J1.9Hz)，7.99(2H，d，J9.0Hz)，7.65(1H，d，J8.7Hz)，7.48(1H，dd，J8.82.0Hz)，6.87(2H，d，J9.1Hz)，3.49(4H，q，J7.0Hz)，2.41(2H，q，J7.5Hz)，1.24-1.14(9H，m)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT 7.24 min MH+352.2；1H NMR(DMSO)：9.97(1H，s)，8.00(1H，d，J1.9Hz)，7.95(2H，d，J9.0Hz)，7.58(1H，d，J8.7Hz)，7.43(1H，dd，J8.82.0Hz)，6.81(2H，d，J9.1Hz)，3.44(4H，q，J7.0Hz)，2.31(2H，t，J7.4Hz)，1.68-1.58(2H，m)，1.15(6H，t，J7.0Hz)，0.94(3H，t，J7.4Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) pentanamide
LCMS RT 7.84 min MH+366.0；1H NMR(DMSO)：9.98(1H，s)，8.00(1H，d，J1.9Hz)，7.95(2H，d，J9.0Hz)，7.58(1H，d，J8.7Hz)，7.42(1H，dd，J8.82.0Hz)，6.81(2H，d，J9.1Hz)，3.44(4H，q，J7.0Hz)，2.33(2H，t，J7.5Hz)，1.65-1.55(2H，m)，1.41-1.28(2H，m)，1.15(6H，t，J7.0Hz)，0.91(3H，t，J7.4Hz)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.25 min MH+352.2；1H NMR(DMSO)：9.99(1H，s)，8.08(1H，d，J1.9Hz)，8.01(2H，d，J9.0Hz)，7.65(1H，d，J8.7Hz)，7.51(1H，dd，J8.82.0Hz)，6.88(2H，d，J9.1Hz)，3.50(4H，q，J7.0Hz)，2.70-2.64(1H，m)，1.24-1.17(12H，m)
N- (2- (4- (diethylamino) phenyl) benzo [ d ] oxazol-5-yl) thiophene-2-carboxamide
LCMS RT 7.77 min, MH+392.1；1H NMR(DMSO)：10.41(1H，s)，8.14(1H，d，J1.8Hz)，8.12(1H，dd，J3.81.0Hz)，8.04(2H，d，J9.1Hz)，7.95(1H，dd，J4.91.0Hz)，7.73(1H，d，J8.6Hz)，7.66(1H，dd，J8.71.9Hz)，7.34-7.30(1H，m)，6.90(2H，d，J9.2Hz)，3.51(4H，q，J7.0Hz)，1.22(6H，t，J7.0Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) isonicotinamide
LCMS RT 6.36 min MH+350.0；1H NMR(DMSO)：10.71(1H，s)，8.82(2H，d，J9.0Hz)，8.32-8.30(1H，m)，8.22(2H，d，J8.6Hz)，7.90(2H，d，J6.0Hz)，7.85-7.79(2H，m)，7.71(2H，d，J8.6Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 7.67 min MH+349.0；1H NMR(DMSO)：10.46(1H，s)，8.32(1H，s)，8.22(2H，d，J8.5Hz)，8.01-7.98(2H，m)，7.79(2H，d，J1.1Hz)，7.71(2H，d，J8.6Hz)，7.65-7.50(3H，m)
4-chloro-N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT 8.51 min MH+383.2；1HNMR(DMSO)：10.52(1H，s)，8.30(1H，s)，8.22(2H，d，J8.8Hz)，8.03(2H，d，J8.8Hz)，7.82-7.77(2H，m)，7.71(2H，d，J8.4Hz)，7.64(2H，d，J8.4Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -4-methylbenzamide
LCMS RT 8.21 min, MH+362.8；1H NMR(DMSO)：10.36(1H，s)，8.31(1H，s)，8.22(2H，d，J8.7Hz)，7.92(2H，d，J8.2Hz)，7.78(2H，d，J1.3Hz)，7.71(2H，d，J8.7Hz)，7.37(2H，d，J8.0Hz)，2.41(3H，s)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -4-methoxybenzamide
LCMS RT 7.62 min MH+378.7；1H NMR(DMSO)：10.28(1H，s)，8.30(1H，s)，8.22(2H，d，J8.9Hz)，7.99(2H，d，J8.9Hz)，7.77(2H，s)，7.70(2H，d，J8.3Hz)，7.08(2H，d，J8.9Hz)，3.86(3H，s)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -2-methoxybenzamide
LCMS RT 8.55 min MH+379.0；1HNMR(DMSO)：10.29(1H，s)，8.29(1H，d，J1.5Hz)，8.18(2H，d，J8.6Hz)，7.77-7.62(5H，m)，7.52-7.46(1H，m)，7.17(1H，d，J8.3Hz)，7.05(1H，t，J7.5Hz)，3.89(3H，s)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -4- (dimethylamino) benzamide
LCMS RT 7.96 min, MH+392.3；1H NMR(DMSO)：10.12(1H，s)，8.36(1H，s)，8.27(2H，d，J8.6Hz)，7.96(2H，d，J8.8Hz)，7.83-7.81(2H，m)，7.76(2H，d，J8.5Hz)，6.84(2H，d，J9.0Hz)，3.07(6H，s)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -4- (trifluoromethyl) benzamide
LCMS RT 8.65 min MH+416.7；1H NMR(DMSO)：10.67(1H，s)，8.32(1H，s)，8.24-8.18(4H，m)，7.95(2H，d，J8.6Hz)，7.84-7.77(2H，m)，7.71(2H，d，J8.6Hz)
3, 5-dichloro-N- (2- (4-diethylamino) phenyl) benzo [ d ] oxazol-5-yl) benzamide
LCMS RT ═ 10.09 minutes, MH+417.1；1H NMR(DMSO)：10.68(1H，s)，8.34(1H，d，J1.8Hz)，8.28(2H，d，J8.6Hz)，8.08(2H，d，J1.9Hz)，7.96(1H，t，J1.9Hz)，7.89-7.78(2H，m)，7.76(2H，d，J8.7Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -4-fluorobenzamide
LCMS RT 7.78 min, MH+367.3；1HNMR(DMSO)：10.58(1H，s)，8.35(1H，s)，8.28(2H，d，J8.9Hz)，8.16-8.11(2H，m)，7.90-7.82(2H，m)，7.77(2H，d，J8.4Hz)，7.52-7.42(2H，m)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -2-phenylacetamide
LCMS RT 7.48 min MH+362.8；1HNMR(DMSO)：10.38(1H，s)，8.22-8.17(3H，m)，7.75-7.65(3H，m)，7.55(1H，dd，J9.02.1Hz)，7.38-7.24(5H，m)，3.69(2H，s)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -3-phenylpropanamide
LCMS RT 7.92 min MH+377.3；1H NMR(DMSO)：10.12(1H，s)，8.19(2H，d，J8.8Hz)，8.16(1H，d，J1.8Hz)，7.74-7.68(3H，m)，7.51(1H，dd，J8.82.0Hz)，7.33-7.17(5H，m)，2.95(2H，t，J7.3Hz)，2.67(2H，t，J7.3Hz)，
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT 7.04 min MH+315.1；1H NMR(DMSO)：10.07(1H，s)，8.21-8.18(3H，m)，7.73-7.67(3H，m)，7.54(1H，dd，J8.81.9Hz)，2.32(2H，t，J7.4Hz)，1.72-1.58(2H，m)，0.94(3H，t，J7.4Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) pentanamide
LCMS RT 7.66 min MH+329.1；1H NMR(DMSO)：10.07(1H，s)，8.22-8.16(3H，m)，7.73-7.68(3H，m)，7.56-7.51(1H，m)，2.34(2H，t，J7.5Hz)，1.66-1.56(2H，m)，1.42-1.30(2H，m)，0.92(3H，t，J7.2Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.04 min MH+315.1；1H NMR(DMSO)：10.03(1H，s)，8.22-8.18(3H，m)，7.74-7.67(3H，m)，7.56(1H，dd，J8.92.1Hz)，2.67-2.59(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) furan-2-carboxamide
LCMS RT ═ 7.01 min, MH+338.9；1H NMR(DMSO)：10.40(1H，s)，8.27(1H，d，J1.1Hz)，8.22(2H，d，J8.5Hz)，7.97(1H，s)，7.78(2H，s)，7.70(2H，d，J8.5Hz)，7.36(1H，d，J3.4Hz)，6.74-6.73(1H，m)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) thiophene-2-carboxamide
LCMS RT 7.54 min MH+355.0；1H NMR(DMSO)：10.42(1H，s)，8.25-8.21(3H，m)，8.06(1H，dd，J3.91.2Hz)，7.89(1H，dd，J5.01.0Hz)，7.80(1H，d，J8.8Hz)，7.74-7.69(3H，m)，7.26(1H，dd，J5.03.8Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) nicotinamide
LCMS RT ═ 6.12 min, MH+330.1；1H NMR(DMSO)：10.62(1H，s)，9.15(1H，dd，J2.10.7Hz)，8.79(1H，dd，J4.81.7Hz)，8.34(1H，dt，J7.91.8Hz)，8.27(1H，d，J1.6Hz)，8.11(2H，d，J8.2Hz)，7.82-7.72(2H，m)，7.63-7.58(1H，m)，7.44(2H，d，J8.0Hz)，2.43(3H，s)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) isonicotinamide
LCMS RT ═ 6.17 min, MH+330.1；1H NMR(DMSO)：10.68(1H，s)，8.82(2H，d，J6.0Hz)，8.27(1H，d，J1.5Hz)，8.22(2H，d，J8.2Hz)，7.90(2H，d，J6.0Hz)，7.81-7.72(2H，m)，7.45(2H，d，J8.0Hz)，2.43(3H，s)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) propanamide
LCMS RT ═ 6.34 min, MH+281.0；1H NMR(DMSO)：10.03(1H，s)，8.14(1H，d，J1.8Hz)，8.08(2H，d，J8.2Hz)，7.69(1H，d，J8.8Hz)，7.51(1H，dd，J8.82.0Hz)，7.44(2H，d，J8.0Hz)，2.42(3H，s)，2.36(2H，q，J7.5Hz)，1.12(3H，t，J7.6Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.73 min, MH+295.1；1H NMR(DMSO)：10.04(1H，s)，8.13(1H，d，J1.8Hz)，8.08(2H，d，J8.2Hz)，7.69(1H，d，J8.8Hz)，7.51(1H，dd，J8.82.0Hz)，7.43(2H，d，J8.0Hz)，2.42(3H，s)，2.32(2H，t，J7.4Hz)，1.71-1.58(2H，m)，0.94(3H，t，J7.4Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) pentanamide
LCMS RT ═ 7.20 min, MH+309.1；1H NMR(DMSO)：10.04(1H，s)，8.13(1H，d，J1.8Hz)，8.08(2H，d，J8.2Hz)，7.68(1H，d，J8.8Hz)，7.51(1H，dd，J8.82.0Hz)，7.43(2H，d，J8.0Hz)，2.42(3H，s)，2.34(2H，t，J7.4Hz)，1.67-1.56(2H，m)，1.41-1.29(2H，m)，0.92(3H，t，J7.4Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.74 min, MH+295.1；1H NMR(DMSO)：10.00(1H，s)，8.15(1H，d，J1.8Hz)，8.09(2H，d，J8.2Hz)，7.69(1H，d，J8.8Hz)，7.53(1H，dd，J8.82.0Hz)，7.43(2H，d，J8.0Hz)，2.66-2.60(1H，m)，2.42(3H，s)，1.13(6H，d，J6.8Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) furan-2-carboxamide
LCMS RT ═ 6.71 min, MH+319.0；1H NMR(DMSO)：10.37(1H，s)，8.23(1H，s)，8.10(2H，d，J8.2Hz)，7.98-7.96(1H，m)，7.75(2H，d，J1.0Hz)，7.44(2H，d，J8.0Hz)，7.36(1H，d，J3.6Hz)，6.74-6.72(1H，m)，2.43(3H，s)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) thiophene-2-carboxamide
LCMS RT 7.15 min MH+335.0；1H NMR(DMSO)：10.40(1H，s)，8.21(1H，d，J1.7Hz)，8.11(2H，d，J8.2Hz)，8.05(1H，dd，J3.81.0Hz)，7.89(1H，d，J4.91.0Hz)，7.76(1H，d，J8.8Hz)，7.69(1H，dd，J8.92.0Hz)，7.44(2H，d，J8.0Hz)，7.26(1H，dd，J5.03.8Hz)，2.43(3H，s)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) nicotinamide
LCMS RT ═ 6.49 min, MH+383.9；1H NMR(DMSO)：10.70(1H，s)，9.20-9.18(1H，m)，8.82(1H，dd，J4.61.5Hz)，8.46(2H，d，J8.1Hz)，8.40-8.36(2H，m)，8.04(2H，d，J8.0Hz)，7.92-7.82(2H，m)，7.66-7.61(1H，m)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) isonicotinamide
LCMS RT 6.52 min;1H NMR(DMSO)：10.80(1H，s)，8.90(2H，d，J6.0Hz)，8.51(2H，d，J8.2Hz)，8.44(1H，d，J1.6Hz)，8.09(2H，d，J8.2Hz)，8.01-7.93(3H，m)，7.89(1H，dd，J8.91.9Hz)
n- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) acetamide
LCMS RT ═ 6.30 min, MH+320.7；1H NMR(DMSO)：10.17(1H，s)，8.40(2H，d，J8.7Hz)，8.22-8.19(1H，m)，7.99(2H，d，J8.5Hz)，7.77(1H，d，J8.7Hz)，7.58-7.53(1H，m)，2.09(3H，s)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT ═ 6.73 min, MH+335.0；1H NMR(DMSO)：10.09(1H，s)，8.40(2H，d，J7.8Hz)，8.23(1H，d，J1.9Hz)，7.99(2H，d，J8.2Hz)，7.77(1H，d，J8.7Hz)，7.57(1H，dd，J8.82.0Hz)，2.37(2H，q，J7.5Hz)，1.12(3H，t，J7.5Hz)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT 7.18 min MH+348.9；1H NMR(DMSO)：10.10(1H，s)，8.40(2H，d，J7.8Hz)，8.23(1H，d，J1.9Hz)，7.99(2H，d，J8.2Hz)，7.77(1H，d，J8.7Hz)，7.58(1H，dd，J8.82.0Hz)，2.33(2H，t，J7.3Hz)，1.69-1.59(2H，m)，0.94(3H，t，J7.6Hz)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) pentanamide
LCMS RT 7.74 min MH+363.1；1H NMR(DMSO)：10.10(1H，s)，8.40(2H，d，J7.8Hz)，8.22(1H，d，J1.9Hz)，7.99(2H，d，J8.2Hz)，7.77(1H，d，J8.7Hz)，7.57(1H，dd，J8.82.0Hz)，2.36(2H，t，J7.3Hz)，1.66-1.58(2H，m)，1.42-1.29(2H，m)，0.92(3H，t，J7.6Hz)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.15 min MH+349.1；1H NMR(DMSO)：10.09(1H，s)，8.43(2H，d，J7.8Hz)，8.27(1H，d，J1.9Hz)，8.02(2H，d，J8.2Hz)，7.80(1H，d，J8.7Hz)，7.63(1H，dd，J8.82.0Hz)，2.72-2.63(1H，m)，1.18(6H，d，J6.8Hz)
N- (2- (4- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) furan-2-carboxamide
LCMS RT 7.15 min MH+373.0；1H NMR(DMSO)：10.28(1H，s)，8.27(2H，d，J8.0Hz)，8.18-8.16(1H，m)，7.86(2H，d，J8.2Hz)，7.84-7.82(1H，m)，7.69-7.67(2H，m)，7.23(1H，dd，J3.50.8Hz)，6.59(1H，dd，J3.51.7Hz)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) isonicotinamide
LCMS RT 5.76 min MH+346.0；1H NMR(DMSO)：10.66(1H，s)，8.81(2H，d，J6.1Hz)，8.24(1H，d，J1.7Hz)，8.16(2H，d，J9.0Hz)，7.90(2H，d，J6.1Hz)，7.77(1H，d，J8.8Hz)，7.72(1H，dd，J8.81.9Hz)，7.18(2H，d，J8.9Hz)，3.88(3H，s)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) acetamide
LCMS RT 5.59 min MH+283.0；1H NMR(DMSO)：10.09(1H，s)，8.13(2H，d，J8.9Hz)，8.08(1H，d，J1.8Hz)，7.67(1H，d，J8.9Hz)，7.47(1H，dd，J8.82.0Hz)，7.16(2H，d，J9.0Hz)，3.87(3H，s)，2.08(3H，s)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT 5.89 min MH+297.1；1H NMR(DMSO)：10.02(1H，s)，8.15-8.10(3H，m)，7.67(1H，d，J8.7Hz)，7.49(1H，dd，J8.81.8Hz)，7.16(2H，d，J8.8Hz)，3.88(3H，s)，2.36(2H，q，J7.7Hz)，1.11(3H，t，J7.5Hz)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.19 min, MH+311.1；1H NMR(DMSO)：10.02(1H，s)，8.13(2H，d，J9.0Hz)，8.10(1H，d，J1.9Hz)，7.66(1H，d，J8.9Hz)，7.49(1H，dd，J8.81.8Hz)，7.16(2H，d，J9.0Hz)，3.87(3H，s)，2.32(2H，t，J7.3Hz)，1.70-1.58(2H，m)，0.94(3H，t，J7.5Hz)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) pentanamide
LCMS RT ═ 6.59 min, MH+325.1；1H NMR(DMSO)：10.02(1H，s)，8.13(2H，d，J9.0Hz)，8.10(1H，d，J1.9Hz)，7.66(1H，d，J8.9Hz)，7.49(1H，dd，J8.81.8Hz)，7.16(2H，d，J9.0Hz)，3.87(3H，s)，2.34(2H，t，J7.3Hz)，1.66-1.56(2H，m)，1.41-1.29(2H，m)，0.92(3H，t，J7.5Hz)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.19 min, MH+311.1；1H NMR(DMSO)：9.98(1H，s)，8.15-8.11(3H，m)，7.66(1H，d，J8.9Hz)，7.51(1H，dd，J8.81.8Hz)，7.16(2H，d，J9.0Hz)，3.88(3H，s)，1.13(6H，d，J6.9Hz)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) furan-2-carboxamide
LCMS RT ═ 6.16 min, MH+335.1；1H NMR(DMSO)：10.36(1H，s)，8.20-8.13(3H，m)，7.96(1H，dd，J1.80.8Hz)，7.72(2H，d，J1.2Hz)，7.36(1H，dd，J3.50.8Hz)，7.17(2H，d，J9.0Hz)，6.73(1H，dd，J3.51.7Hz)，3.88(3H，s)
N- (2- (4-methoxyphenyl) benzo [ d ] oxazol-5-yl) thiophene-2-carboxamide
LCMS RT ═ 6.54 min, MH+351.0；1H NMR(DMSO)：10.38(1H，s)，8.19-8.14(3H，m)，8.05(1H，dd，J3.71.0Hz)，7.88(1H，dd，J4.11.0Hz)，7.74(1H，d，J8.8Hz)，7.67(1H，dd，J8.82.0Hz)，121-123(1H，m)，7.17(2H，d，J8.9Hz)，3.88(3H，s)
N- (2-m-tolylbenzo [ d ] oxazol-5-yl) butanamide
LCMS RT 6.67 min MH+295.0；
N- (2- (3- (dimethylamino) phenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.62 min, MH+324.1；1H NMR(DMSO)：10.06(1H，s)，8.13(1H，d，J1.8Hz)，7.70(1H，d，J8.8Hz)，7.53(1H，dd，J8.82.0Hz)，7.49-7.37(3H，m)，7.00-6.96(1H，m)，3.00(6H，s)，2.32(2H，t，J7.6Hz)，1.71-1.55(2H，m)，0.94(3H，t，J7.4Hz)
N- (2-m-tolylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 6.64 min MH+295.0；1HNMR(DMSO)：10.02(1H，s)，8.17(1H，d，J1.9Hz)，8.03-7.98(2H，m)，7.71(1H，d，J8.8Hz)，7.56-7.44(3H，m)，2.60-2.58(1H，m)，2.44(3H，s)，1.14(6H，d，J6.8Hz)
N- (2- (3- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.88 min, MH+349.0；1H NMR(DMSO)：10.06(1H，s)，8.51-8.43(2H，m)，8.23(1H，s)，8.03(1H，d，J7.4Hz)，7.91-7.85(1H，m)，7.77(1H，d，J8.5Hz)，7.62-7.57(1H，m)，2.63(1H，t，J6.8Hz)，1.14(6H，d，J6.8Hz)
N- (2- (3- (dimethylamino) phenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.59 min, MH+324.1；1H NMR(DMSO)：10.01(1H，s)，8.15(1H，d，J1.8Hz)，7.70(1H，d，J8.8Hz)，7.55(1H，dd，J8.82.0Hz)，7.49-7.37(3H，m)，7.00-6.96(1H，m)，3.01(6H，s)，2.65-2.58(1H，m)，1.13(6H，d，J7.0Hz)
N- (2- (3- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.85 min, MH+349.0；1H NMR(DMSO)：10.08(1H，s)，8.48(1H，d，J7.8Hz)，8.43(1H，s)，8.21(1H，d，J1.9Hz)，8.02(1H，d，J8.0Hz)，7.88(1H，d，J7.7Hz)，7.76(1H，d，J8.8Hz)，7.58(1H，dd，J8.82.0Hz)，2.33(2H，t，J7.4Hz)，1.71-1.59(2H，m)，0.95(3H，t，J7.4Hz)
N- (2-o-tolylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.62 min, MH+295.1；1H NMR(DMSO)：10.00(1H，s)，8.19(1H，d，J1.9Hz)，8.12(1H，dd，J7.41.5Hz)，7.71(1H，d，J8.8Hz)，7.57-7.40(4H，m)，2.75(3H，s)，2.65-2.59(1H，m)，1.14(6H，d，J6.7Hz)
N- (2- (2-chlorophenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.42 min, MH+315.0；1H NMR(DMSO)：10.08(1H，s)，8.22(1H，d，J1.8Hz)，8.15(1H，dd，J7.61.8Hz)，7.76-7.55(5H，m)，2.34(2H，t，J7.4Hz)，1.71-1.59(2H，m)，0.95(3H，t，J7.4Hz)
N- (2- (2-chlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.41 min, MH+315.0；1H NMR(DMSO)：10.03(1H，s)，8.23(1H，d，J1.8Hz)，8.15(1H，dd，J7.61.7Hz)，7.71-7.55(5H，m)，2.68-2.58(1H，m)，1.14(6H，d，J6.7Hz)
N- (2- (3-chlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.89 min, MH+315.0；1H NMR(DMSO)：10.05(1H，s)，8.21-8.15(3H，m)，7.75-7.63(3H，m)，7.57(1H，d，J8.82.0Hz)，2.62-2.58(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (3-chlorophenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.89 min, MH+315.1；1H NMR(DMSO)：10.07(1H，s)，8.19-8.11(3H，m)，7.75-7.63(3H，m)，7.56(1H，d，J8.82.0Hz)，2.33(2H，t，J7.4Hz)，1.71-1.59(2H，m)，0.94(3H，t，J7.4Hz)
Method 3C (Compound II)
The procedure was as in method 3A except that diisopropylamine dissolved in dichloromethane was replaced with pyridine as solvent and base.
N- (2-Phenyloxazolo [5, 4-b ] pyridinyl-6-yl) butanamide
LCMS RT 5.95 min MH+282.0；1H NMR(DMSO)：10.31(1H，s)，8.54(1H，d，J2.3Hz)，8.48(1H，d，J2.3Hz)，8.24-8.21(2H，m)，7.72-7.62(3H，m)，2.37(2H，t，J7.3Hz)，1.72-1.60(2H，m)，0.95(3H，t，J7.5Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT ═ 6.54 min, MH+301.0；1H NMR(DMSO)：10.07(1H，s)，8.21-8.18(3H，m)，7.73-7.67(3H，m)，7.53(1H，dd，J8.82.0Hz)，2.36(2H，q，J7.6Hz)，1.12(3H，t，J7.5Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) palmitamide
LCMS RT ═ 6.94 min, MH+309.1；1H NMR(DMSO)：9.36(1H，s)，8.13(1H，d，J1.8Hz)，8.09(2H，d，J8.2Hz)，7.69(1H，d，J8.8Hz)，7.61(1H，dd，J8.82.0Hz)，7.43(2H，d，J8.0Hz)，2.42(3H，s)，1.26(9H，s)
N- (2- (4-chlorophenyl) benzo [ d ] oxazolyl-5-yl) palmitamide
LCMS RT 7.28 min MH+329.1；1H NMR(DMSO)：9.39(1H，s)，8.20(2H，d，J8.6Hz)，8.17(1H，d，J1.7Hz)，7.74-7.62(4H，m)，1.26(9H，s)
N- (2-benzylbenzo [ d ] oxazol-5-yl) butanamide
LCMS RT 5.98 min MH+295.1；1H NMR(DMSO)：9.97(1H，s)，8.03(1H，d，J1.8Hz)，7.56(1H，d，J8.7Hz)，7.44(1H，dd，J8.92.1Hz)，7.38-7.35(4H，m)，7.33-7.25(1H，m)，4.31(2H，s)，2.28(2H，t，J7.3Hz)，1.69-1.53(2H，m)，0.92(3H，t，J7.5Hz)
N- (2-benzylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.96 min MH+295.1；1H NMR(DMSO)：9.93(1H，s)，8.04(1H，d，J2.1Hz)，7.56(1H，d，J8.9Hz)，7.47(1H，dd，J9.02.0Hz)，7.38-7.35(4H，m)，7.33-7.28(1H，m)，4.31(2H，s)，2.60-2.58(1H，m)，1.11(6H，d，J6.8Hz)
N- (2-p-tolylbenzo [ d ] oxazolyl-4-yl) butanamide
LCMS RT 7.54 min MH+295.1；1H NMR(DMSO)：10.03(1H，s)，8.13(2H，d，J8.2Hz)，8.03(1H，d，J8.2Hz)，7.48-7.44(3H，m)，7.34(1H，t，J8.2Hz)，2.43(3H，s)，1.72-1.60(2H，m)，1.09(3H，t，J6.9Hz)
N- (2-p-tolylbenzo [ d ] oxazolyl-4-yl) isobutyramide
LCMS RT 7.51 min MH+295.1；1H NMR(DMSO)：9.78(1H，s)，7.93(2H，d，J8.4Hz)，7.83(1H，d，J8.2Hz)，7.28-7.23(3H，m)，7.14(1H，t，J8.4Hz)，2.22(3H，s)，0.94(6H，d，J6.8Hz)
N- (2-cyclohexylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 6.48 min MH+287.1；1H NMR(CDCl3)：7.82(1H，d，J1.7Hz)，7.66-7.56(1H，m)，7.46(1H，d，J8.8Hz)，7.30-7.25(1H，m)，3.07-2.97(1H，m)，2.65-2.53(1H，m)，2.26-2.16(2H，m)，1.97-1.72(5H，m)，1.56-1.37(3H，m)，1.33(6H，t，J6.8Hz)
N- (2-cyclohexylbenzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.51 min, MH+287.2；1H NMR(CDCl3)：7.69(1H，s)，7.45(1H，d，J8.8Hz)，7.33(1H，d，J8.8Hz)，7.16(1H，s)，2.93-2.83(1H，m)，2.29(2H，t，J7.6Hz)，2.11-2.06(2H，m)，1.83-1.57(6H，m)，1.43-1.18(4H，m)，0.95(3H，t，J7.5Hz)
N- (2- (2, 4-dichlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.17 min MH+348.9；1H NMR(DMSO)：10.11(1H，s)，8.23(1H，d，J1.7Hz)，8.19(1H，d，J8.8Hz)，7.92(1H，d，J2.1Hz)，7.75(1H，d，J9.0Hz)，7.68(1H，dd，J8.52.1Hz)，7.60(1H，dd，J8.72.0Hz)，2.64(1H，t，J6.8Hz)，1.14(6H，d，J6.8Hz)
N- (2- (4-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.39 min, MH+299.0；1H NMR(DMSO)：10.00(1H，s)，8.27-8.23(2H，m)，8.18-8.17(1H，m)，7.70(1H，d，J8.6Hz)，7.55(1H，dd，J8.72.0Hz)，7.46(2H，t，J8.7Hz)，2.64-2.59(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (3, 4-dichlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.55 min MH+349.5；1H NMR(DMSO)：10.03(1H，s)，8.35(1H，d，J1.9Hz)，8.21(1H，d，J1.9Hz)，8.15(1H，d，J8.42.0Hz)，7.89(1H，d，J8.4Hz)，7.74(1H，d，J8.9Hz)，7.58(1H，dd，J8.92.0Hz)，2.67-2.60(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (5-chloropyridin-2-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.95 min MH+316.0；1H NMR(DMSO)：10.05(1H，s)，8.86(1H，d，J2.1Hz)，8.35(1H，d，J8.5Hz)，8.25(1H，d，J1.7Hz)，8.19(1H，dd，J8.52.4Hz)，7.77(1H，d，J8.8Hz)，7.60(1H，dd，J8.82.0Hz)，2.65-2.61(1H，m)，1.14(6H，d，J6.7Hz)
N- (2- (3, 5-dichlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.83 min, MH+348.7；1H NMR(DMSO)：10.05(1H，s)，8.23(1H，d，J1.9Hz)，8.15(2H，d，J2.0Hz)，7.92(1H，t，J2.0Hz)，7.75(1H，d，J8.8Hz)，7.60(1H，dd，J8.92.0Hz)，2.68-2.60(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (2, 3-dichlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.80 min, MH+348.9；1H NMR(DMSO)：10.04(1H，s)，8.24(1H，d，J1.8Hz)，8.11(1H，dd，J7.91.6Hz)，7.93(1H，dd，J8.11.6Hz)，7.76(1H，d，J8.8Hz)，7.63-7.59(2H，m)，2.70-2.58(1H，m)，1.14(6H，d，J6.8Hz)
N- (2-phenethylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.22 min, MH+309.1；1H NMR(DMSO)：9.92(1H，s)，8.03(1H，d，J1.8Hz)，7.57(1H，d，J8.8Hz)，7.46(1H，dd，J8.72.0Hz)，7.29-7.27(4H，m)，7.23-7.16(1H，m)，3.21-3.10(4H，m)，1.12(6H，d，J6.7Hz)
N- (2- (1-phenylethyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.23 min, MH+309.1；1H NMR(DMSO)：9.93(1H，s)，8.06(1H，d，J1.9Hz)，7.54(1H，d，J8.8Hz)，7.47(1H，dd，J8.82.1Hz)，7.36-7.32(4H，m)，7.30-7.24(1H，m)，4.51(1H，q，J7.1Hz)，2.65-2.57(1H，m)，1.71(3H，d，J7.2Hz)，1.12(6H，d，J6.8Hz)
N- (2- (2, 5-dichlorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 7.10 min, MH+349.0；1H NMR(DMSO)：10.11(1H，s)，8.31(1H，d，J1.8Hz)，8.25(1H，dd，J2.40.5Hz)，7.83(2H，d，J8.7Hz)，7.80(1H，dd，J8.72.5Hz)，7.67(1H，dd，J8.92.0Hz)，2.74-2.64(1H，m)，1.20(6H，d，J6.8Hz)
N- (2- (2-chloro-4-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.59 min, MH+333.0；1H NMR(DMSO)：10.05(1H，s)，8.30-8.20(2H，m)，7.77-7.73(2H，m)，7.59(1H，dd，J8.82.0Hz)，7.51-7.45(1H，m)，2.68-2.57(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (2-chloro-6-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.29 min, MH+333.1；1H NMR(DMSO)：10.08(1H，s)，8.26(1H，d，J1.9Hz)，7.80-7.71(2H，m)，7.64-7.60(2H，m)，7.57-7.50(1H，m)，2.68-2.58(1H，m)，1.14(6H，d，J6.9Hz)
N- (2- (3-chloro-2-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.65 min, MH+333.1；1H NMR(DMSO)：10.06(1H，s)，8.31-8.16(2H，m)，7.88(1H，dt，J8.41.7Hz)，7.77(1H，d，J8.8Hz)，7.60(1H，dd，J8.92.0Hz)，7.47(1H，dt，J8.01.0Hz)，2.66-2.60(1H，m)，1.14(6H，d，J6.7Hz)
N- (2- (4-chloro-2-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.69 min, MH+333.1；1H NMR(DMSO)：10.05(1H，s)，8.28-8.21(2H，m)，7.79-7.73(2H，m)，7.60-7.53(2H，m)，2.67-2.58(1H，m)，1.14(6H，d，J6.7Hz)
N- (2- (2-chloro-5-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.54 min, MH+333.1；1H NMR(DMSO)：10.07(1H，s)，8.25(1H，d，J1.9Hz)，7.99(1H，dd，J9.23.2Hz)，7.80-7.75(2H，m)，7.63-7.52(2H，m)，2.68-2.59(1H，m)，1.14(6H，d，J6.7Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) cyclopentanecarboxamide
LCMS RT 7.52 min MH+341.0；1H NMR(DMSO)：10.08(1H，s)，8.20-8.16(3H，m)，7.73-7.66(3H，m)，7.55(1H，dd，J8.82.0Hz)，2.85-2.75(1H，m)，1.93-1.57(8H，m)
N- (5-chloro-2 (4-chlorophenyl) benzo [ d ] oxazol-6-yl) isobutyramide
LCMS RT 8.10 min;1H NMR(DMSO)：9.59(1H，s)，8.20(2H，d，J8.8Hz)，8.12(1H，s)，8.02(1H，s)，7.71(2H，d，J8.6Hz)，2.84-2.73(1H，m)，1.16(6H，d，J6.8Hz)
n- (2- (tetrahydro-2H-pyran-4-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.38 min MH+289.0；1H NMR(DMSO)：9.95(1H，s)，8.04(1H，d，J1.9Hz)，7.59(1H，d，J8.8Hz)，7.48(1H，dd，J8.82.0Hz)，3.95-3.88(2H，m)，3.47-3.43(3H，m)，2.64-2.55(1H，m)，2.06-1.99(2H，m)，1.89-1.75(2H，m)，1.12(6H，d，J6.8Hz)
N- (2- (3, 4-dichlorophenyl) benzo [ d ] oxazol-5-yl) cyclopropanecarboxamide
LCMS RT ═ 6.99 min, MH+348.8；1H NMR(DMSO)：10.45(1H，s)，8.30(1H，dd，J2.0Hz)，8.15(1H，d，J1.9Hz)，8.10(1H，dd，J8.42.0Hz)，7.86(1H，d，J8.4Hz)，7.71(1H，d，J8.9Hz)，7.53(1H，dd，J8.92.0Hz)，1.81-1.74(1H，m)，0.82-0.76(4H，m)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-6-yl) cyclopropanecarboxamide
LCMS RT ═ 6.93 min, MH+312.9；1H NMR(DMSO)：10.53(1H，s)，8.27(1H，dd，J1.7Hz)，8.18(2H，d，J8.7Hz)，7.74(1H，d，J8.7Hz)，7.68(2H，d，J8.7Hz)，7.44(1H，dd，J8.71.9Hz)，1.86-1.78(1H，m)，0.85-0.80(4H，m)
N- (2- (2, 3-dichlorophenyl) benzo [ d ] oxazol-6-yl) isobutyramide
LCMS RT 7.05 min;1H NMR(DMSO)：10.21(1H，s)，8.34(1H，d，J1.8Hz)，8.11(1H，dd，J7.91.6Hz)，7.92(1H，dd，J8.11.5Hz)，7.81(1H，d，J8.7Hz)，7.60(1H，t，J8.0Hz)，7.48(1H，dd，J8.71.9Hz)，2.67-2.61(1H，m)，1.14(6H，d，J6.8Hz)
n- (2- (4- (trifluoromethoxy) phenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.04 min;1H NMR(DMSO)：10.05(1H，s)，8.32(2H，d，J9.0Hz)，8.20(1H，d，J1.9Hz)，7.74(1H，d，J8.9Hz)，7.63-7.55(3H，m)，2.68-2.57(1H，m)，1.14(6H，d，J6.8Hz)
n- (2-cyclopentylbenzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.23 min MH+273.0；1H NMR(DMSO)：9.93(1H，s)，8.01(1H，d，J1.8Hz)，7.57(1H，d，J8.7Hz)，7.46(1H，dd，J8.81.8Hz)，3.42-3.39(1H，m)，2.61-2.57(1H，m)，2.15-2.04(2H，m)，1.95-1.87(2H，m)，1.78-1.62(4H，m)，1.12(6H，d，J6.8Hz)
N- (4- (5-acetamidobenzo [ d ] oxazol-2-yl) phenyl) acetamide
LCMS RT＝5.0SnUn5MH+309.9；1H NMR(DMSO)：10.31(1H，s)，10.11(1H，s)，8.13-8.08(3H，m)，7.82(2H，d，J8.7Hz)，7.68(1H，d，J8.7Hz)，7.48(1H，dd，J8.82.0Hz)，2.11(3H，s)，2.08(3H，s)
N- (2- (2-chloro-3- (trifluoromethyl) phenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.78 min, MH+383.0；1H NMR(DMSO)：10.07(1H，s)，8.40(1H，dd，J8.11.3Hz)，8.27(1H，d，J1.8Hz)，8.14(1H，dd，J7.91.3Hz)，7.82-7.77(2H，m)，7.62(1H，dd，J8.82.1Hz)，2.66-2.61(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (3, 4-dichlorophenyl) benzo [ d ] oxazol-6-yl) isobutyramide
LCMS RT 7.82 min MH+349.1；1H NMR(DMSO)：10.20(1H，s)，8.33(1H，d，J2.0Hz)，8.31(1H，d，J1.7Hz)，8.14(1H，dd，J8.42.0Hz)，7.88(1H，d，J8.5Hz)，7.75(1H，d，J8.8Hz)，7.48(1H，dd，J8.71.9Hz)，2.68-2.60(1H，m)，1.14(6H，d，J6.8Hz)
N- (2- (naphthalen-2-yl) benzo [ d ] oxazol-5-yl) acetamide
LCMS RT ═ 6.45 min, MH+303.1；1H NMR(DMSO)：10.15(1H，s)，8.84(1H，s)，8.27(1H，dd，J8.61.7Hz)，8.20-8.13(3H，m)，8.06-8.03(1H，m)，7.76(1H，d，J8.6Hz)，7.71-7.63(2H，m)，7.54(1H，dd，J8.82.1Hz)，2.17(3H，s)
N- (2- (4-acetamidophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.52 min MH+338.0；1H NMR(DMSO)：10.46(1H，s)，10.31(1H，s)，8.15-8.11(3H，m)，7.82(2H，d，J8.7Hz)，7.67(1H，d，J8.7Hz)，7.52(1H，dd，J8.81.9Hz)，2.67-2.58(1H，m)，2.11(3H，s)，1.13(6H，d，J6.9Hz)
N- (2- (naphthalen-2-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 7.10 min, MH+331.1；1H NMR(DMSO)：10.04(1H，s)，8.84(1H，s)，8.28-8.12(4H，m)，8.07-8.03(1H，m)，7.76(1H，d，J8.9Hz)，7.77-7.62(2H，m)，7.58(1H，dd，J8.82.1Hz)，2.64(1H，t，J7.4Hz)，1.15(6H，d，J6.9Hz)
N- (2- (naphthalen-2-yl) benzo [ d ] oxazol-5-yl) thiophene-2-carboxamides
LCMS RT 7.47 min MH+370.8；1H NMR(DMSO)：10.44(1H，s)，8.86(1H，s)，8.30-8.14(4H，m)，8.08-8.04(2H，m)，7.89(1H，dd，J5.01.0Hz)，7.83(1H，d，J8.8Hz)，7.76-7.64(3H，m)，7.28-7.25(1H，m)
N- (2- (naphthyl-1-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.25 min MH+331.2；1H NMR(DMSO)：10.07(1H，s)，9.42(1H，dd，J8.20.7Hz)，8.45(1H，dd，J7.41.2Hz)，8.29(1H，d，J1.9Hz)，8.26-8.21(1H，m)，8.13-8.09(1H，m)，7.81-7.66(4H，m)，7.61(1H，dd，J8.82.1Hz)，2.70-2.61(1H，m)，1.16(6H，d，J6.8Hz)
N- (2- (biphenyl-4-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.56 min MH+357.3；1H NMR(DMSO)：10.03(1H，s)，8.28(2H，d，J8.5Hz)，8.20(1H，d，J2.0Hz)，7.94(2H，d，J8.6Hz)，7.82-7.78(2H，m)，7.74(1H，d，J8.8Hz)，7.58-7.41(4H，m)，2.68-2.59(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (6-methoxy-2-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.02 min, MH+361.2；1H NMR(DMSO)：10.03(1H，s)，8.75(1H，d，J0.8Hz)，8.21(2H，dd，J8.91.6Hz)，8.10(1H，d，J9.0Hz)，8.02(1H，d，J8.7Hz)，7.73(1H，d，J8.7Hz)，7.56(1H，dd，J8.82.0Hz)，7.46(1H，d，J2.3Hz)，7.29(1H，dd，J8.82.5Hz)，3.93(3H，s)，2.68-2.58(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (6-bromonaphthalen-2-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 8.13 min MH+411.1；1H NMR(DMSO)：10.06(1H，s)，8.86(1H，s)，8.36(1H，d，J1.7Hz)，8.31(1H，d，J8.71.7Hz)，8.23(1H，d，J1.9Hz)，8.18(1H，d，J8.9Hz)，8.13(1H，d，J8.7Hz)，7.80-7.74(2H，m)，7.58(1H，dd，J8.92.2Hz)，2.68-2.59(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (quinolin-3-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.24 min, MH+332.2；1H NMR(DMSO)：10.08(1H，s)，9.62(1H，d，J2.1Hz)，9.22(1H，d，J1.9Hz)，8.29-8.24(2H，m)，8.15(1H，d，J8.6Hz)，7.95-7.90(1H，m)，7.80-7.73(2H，m)，7.61(1H，dd，J8.82.2Hz)，2.69-2.60(1H，m)，1.15(6H，d，J6.9Hz)
N- (2- (quinolin-2-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.28 min, MH+332.2；1H NMR(DMSO)：10.09(1H，s)，8.64(1H，d，J8.4Hz)，8.45(1H，d，J8.5Hz)，8.32(1H，d，J1.8Hz)，8.22(1H，d，J8.7Hz)，8.13(1H，dd，J8.50.9Hz)，7.94-7.84(2H，m)，7.78-7.73(1H，m)，7.63(1H，dd，J8.82.0Hz)，2.69-2.60(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (4-cyclohexylphenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 8.87 min MH+363.3；1H NMR(DMSO)：10.00(1H，s)，8.15(1H，d，J1.9Hz)，8.11(2H，d，J8.4Hz)，7.69(1H，d，J8.7Hz)，7.53(1H，dd，J8.82.1Hz)，7.47(2H，d，J8.3Hz)，2.67-2.58(2H，m)，1.84-1.71(5H，m)，1.52-1.23(5H，m)，1.13(6H，d，J6.8Hz)
N- (2- (benzo [ d ] [ l, 3] dioxol-5-yl) -5-chlorobenzo [ d ] oxazol-6-yl) isobutyramide
1H NMR(DMSO)：9.56(1H，s)，8.05(1H，s)，7.94(1H，s)，7.77(1H，dd，J8.11.7Hz)，7.64(1H，d，J1.6Hz)，7.16(1H，d，J8.2Hz)，6.19(2H，s)，2.83-2.72(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (furan-2-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 5.75 min MH+271.1；1H NMR(DMSO)：9.95(1H，s)，8.08(1H，d，J1.8Hz)，8.01(1H，dd，J1.70.7Hz)，7.62(1H，d，J8.9Hz)，7.47(1H，dd，J8.92.0Hz)，7.39(1H，dd，J3.50.7Hz)，6.75(1H，dd，J3.51.8Hz)，2.60-2.50(1H，m)，1.07(6H，d，J6.8Hz)
N- (4- (naphtho [ l, 2-d ] oxazol-2-yl) phenyl) isobutyramide
LCMS RT 7.49 min MH+331.1；1H NMR(DMSO)：10.22(1H，s)，8.45(1H，d，J8.1Hz)，8.22(2H，d，J8.7Hz)，8.13(1H，d，J8.5Hz)，7.98(2H，s)，7.89(2H，d，J8.9Hz)，7.77-7.70(1H，m)，7.65-7.59(1H，m)，2.69-2.60(1H，m)，1.14(6H，d，J6.7Hz)
N- (4- (benzo [ d ] oxazol-2-yl) phenyl) isobutyramide
LCMS RT 6.48 min MH+281.1；1H NMR(DMSO)：10.23(1H，s)，8.14(2H，d，J8.9Hz)，7.86(2H，d，J8.8Hz)，7.79-7.75(2H，m)，7.42-7.38(2H，m)，2.70-2.60(1H，m)，1.13(6H，d，J6.8Hz)
Method 3D (Compound II)
As in method 3A except that diisopropylethylamine dissolved in dichloromethane was replaced with pyridine dissolved in dichloromethane.
N- (2- (2-fluorophenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.10 min, MH+299.0；1H NMR(DMSO)：10.07(1H，s)，8.25-8.19(2H，m)，7.75(1H，d，J8.8Hz)，7.72-7.66(1H，m)，7.58-7.42(3H，m)，2.33(2H，t，J7.5Hz)，1.71-1.59(2H，m)，0.94(3H，t，J7.4Hz)
N- (2- (2-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.09 minutes, MH+299.0；1H NMR(DMSO)：10.09(1H，s)，8.31-8.25(2H，m)，7.81(1H，d，J8.8Hz)，7.78-7.72(1H，m)，7.64(1H，d，J8.71.8Hz)，7.58-7.48(2H，m)，2.74-2.65(1H，m)，1.20(6H，d，J6.8Hz)
N- (2- (3-fluorophenyl) benzo [ d ] oxazol-5-yl) butanamide
LCMS RT ═ 6.39 min, MH+299.0；1H NMR(DMSO)：10.12(1H，s)，8.24(1H，d，J1.9Hz)，8.12-8.08(1H，m)，8.02-7.97(1H，m)，7.79(1H，d，J8.8Hz)，7.75-7.70(1H，m)，7.63-7.53(2H，m)，2.38(2H，t，J7.4Hz)，1.77-1.64(2H，m)，1.00(3H，t，J7.4Hz)
N- (2- (3-fluorophenyl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.37 minutes, MH+299.0；1H NMR(DMSO)：10.08(1H，s)，8.26(1H，d，J1.9Hz)，8.12-8.08(1H，m)，8.02-7.97(1H，m)，7.79(1H，d，J9.0Hz)，7.75-7.69(1H，m)，7.63(1H，dd，J8.81.9Hz)，7.59-7.52(1H，m)，2.73-2.66(1H，m)，1.19(6H，d，J6.9Hz)
N- (2- (benzo [ d ] [ l, 3] dioxol-5-yl) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT ═ 6.14 min, MH+324.9；1H NMR(DMSO)：10.04(1H，s)，8.18(1H，d，J1.8Hz)，7.82(1H，dd，J8.21.8Hz)，7.73-7.69(2H，m)，7.58(1H，dd，J8.72.0Hz)，7.20(1H，d，J8.2Hz)，6.24(2H，s)，2.72-2.65(1H，m)，1.19(6H，d，J6.9Hz)
2- (4-chlorophenyl) benzo [ d ] oxazol-5-ylcarbamic acid ethyl ester
LCMS RT 7.14 min MH+317.1；1H NMR(DMSO)：9.80(1H，s)，8.18(2H，d，J8.6Hz)，7.96(1H，d，J1.7Hz)，7.71-7.67(3H，m)，7.45(1H，dd，J8.82.0Hz)，4.16(2H，q，J7.2Hz)，1.27(3H，t，J7.1Hz)
Method 3E (Compound II)
As in method 3C except that a piece of DMAP was added to the reaction.
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-6-yl) isobutyramide
LCMS RT 7.07 min, MH+314.9；1H NMR(DMSO)：10.15(1H，s)，8.29(1H，d，J1.7Hz)，8.18(2H，d，J8.8Hz)，7.73(1H，d，J8.7Hz)，7.68(2H，d，J8.7Hz)，7.49(1H，dd，J8.71.9Hz)，2.64(1H，t，J6.8Hz)，1.14(6H，d，J6.8Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-6-yl) butanamide
LCMS RT 7.07 min, MH+314.9；1H NMR(DMSO)：10.20(1H，s)，8.29(1H，d，J1.7Hz)，8.18(2H，d，J8.8Hz)，7.73(1H，d，J8.7Hz)，7.68(2H，d，J8.7Hz)，7.43(1H，dd，J8.71.9Hz)，2.34(2H，t，J7.3Hz)，1.71-1.59(2H，m)，0.94(3H，t，J7.4Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) cyclopropanecarboxamide
LCMS RT ═ 6.69 min, MH+313.1；1H NMR(DMSO)：10.39(1H，s)，8.20-8.15(3H，m)，7.74-7.68(3H，m)，7.54(1H，d，J8.92.1Hz)，1.84-1.76(1H，m)，0.81-0.78(4H，m)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) cyclobutanecarboxamide
LCMS RT 7.07 min, MH+327.0；1H NMR(DMSO)：9.91(1H，s)，8.21-8.17(3H，m)，7.73-7.67(3H，m)，7.55(1H，d，J8.92.1Hz)，2.33-1.81(7H，m)
Method 3F (Compound II)
4, 4, 4-trifluoro-N- (2-p-tolylbenzo [ d ] oxazol-5-yl) butanamide
HATU (397mg, 1.05mmol) and diisopropylethylamine (496. mu.L, 2.85mmol) were added to 4, 4, 4-trifluorobutanoic acid (128mg, 0.90mmol) in anhydrous dimethylformamide (5 mL). The mixture was then stirred at room temperature for 10 minutes. Then 2-p-tolylbenzo [ d ] was added]To oxazol-5-amine (200mg, 0.95mmol), the resulting mixture was stirred at room temperature for 16 hours. Adding ethyl acetate and adding Na2CO3The organic layer was washed once with a saturated aqueous solution, followed by washing with brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography (eluting with ethyl acetate/hexanes-40: 60 v/v) to give 26.7mg (8%) of the title compound (LCMS RT-6.77 min, MH)+348.9)。
1H NMR(DMSO)：10.28(1H，s)，8.12(1H，d，J1.9Hz)，8.08(2H，d，J8.2Hz)，7.72(1H，d，J8.8Hz)，7.50(1H，dd，J8.82.1Hz)，7.43(2H，d，J8.1Hz)，2.67-2.56(4H，m)，2.42(3H，s)
The following compounds were prepared using the same general procedure.
3-methoxy-N- (2-p-tolylbenzo [ d ] oxazol-5-yl) propanamide
LCMS RT ═ 6.03 min, MH+311.0；1H NMR(DMSO)：10.13(1H，s)，8.14(1H，d，J2.2Hz)，8.08(2H，d，J8.4Hz)，7.70(1H，d，J8.9Hz)，7.52(1H，dd，J8.92.0Hz)，7.43(2H，d，J8.3Hz)，3.65(2H，t，J6.2Hz)，3.26(3H，s)，2.61-2.56(2H，m)，2.42(3H，s)
Tert-butyl-3-oxo-3- (2-phenylbenzo [ d ] oxazol-5-ylamino) propylcarbamate
LCMS RT ═ 6.22 min, MH+382.0；1H NMR(CDCl3)：8.19-8.14(2H，m)，7.89(2H，s)，7.50-7.42(5H，m)，5.15-5.05(1H，br)，3.49-3.43(2H，m)，2.59(2H，t，J7.6Hz)，1.38(9H，s)
3, 3, 3-trifluoro-N- (2-p-tolylbenzo [ d ] oxazol-5-yl) propanamide
LCMS RT ═ 14.01 min, MH+335.0；1H NMR(DMSO)：10.48(1H，s)，8.11-8.08(3H，m)，7.75(1H，d，J9.0Hz)，7.49(1H，dd，J8.72.1Hz)，7.44(2H，d，J8.0Hz)，3.55(2H，q，J10.9Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -3-methoxypropionamide
LCMS RT ═ 6.32 min, MH+331.1；1H NMR(DMSO)：10.17(1H，s)，8.22-8.17(3H，m)，7.74-7.68(3H，m)，7.54(1H，dd，J8.92.1Hz)，3.65(2H，t，J6.1Hz)，3.26(3H，s)，2.59(2H，t，J6.1Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -3, 3, 3-trifluoropropionamide
LCMS RT ═ 6.72 min, MH+354.7；1H NMR(DMSO)：10.52(1H，s)，8.21(2H，d，J8.7Hz)，8.14(1H，d，J2.0Hz)，7.78(1H，d，J8.7Hz)，7.70(2H，d，J8.7Hz)，7.52(1H，dd，J8.82.1Hz)，3.56(2H，q，J11.1Hz)
N- (2- (3, 4-dichlorophenyl) benzo [ d ] oxazol-5-yl) -3, 3, 3-trifluoropropionamide
LCMS RT 7.41 min MH+388.8；1H NMR(DMSO)：10.54(1H，s)，8.36(1H，d，J2.0Hz)，8.17-8.14(2H，m)，7.90(1H，d，J8.4Hz)，7.80(1H，d，J8.8Hz)，7.54(1H，dd，J8.92.1Hz)，3.56(2H，q，J11.1Hz)
N- (2- (2, 3-dichlorophenyl) benzo [ d ] oxazol-5-yl) -3, 3, 3-trifluoropropionamide
LCMS RT ═ 6.76 min, MH+388.9；1H NMR(DMSO)：10.55(1H，s)，8.20(1H，d，J1.9Hz)，8.12(1H，dd，J7.91.6Hz)，7.94(1H，dd，J8.11.6Hz)，7.83(1H，d，J8.8Hz)，7.64-7.55(2H，m)，3.58(2H，q，J11.1Hz)
The following compounds were prepared using method 3F using the appropriate Boc-amino acid. After coupling, the Boc group was deprotected with 4M HCl in dioxane at room temperature.
(S) -N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) pyrrolidine-2-carboxamide
LCMS RT 4.54 min MH+342.0；1H NMR(DMSO)：10.15(1H，s)，8.23(1H，d，J1.7Hz)，8.19(2H，d，J8.7Hz)，7.74-7.63(4H，m)，3.75-3.69(1H，m)，2.91(2H，t，J6.5Hz)，2.12-2.00(1H，m)，1.90-1.60(3H，m)
(S) -N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -2- (methylamino) propionamide
LCMS RT 4.46 min MH+330.1；1H NMR(DMSO)：8.20-8.10(3H，m)，7.67(2H，d，J8.8Hz)，7.58-7.47(2H，m)，3.00(1H，q，J6.8Hz)，2.24(3H，s)，1.16(3H，d，J6.8Hz)
The following compounds were prepared using method 3F using the appropriate Fmoc-amino acids. After coupling, the Fmoc group was deprotected with piperidine/DMF ═ 20:80 v/v.
(S) -2-amino-N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) propanamide
LCMS RT 4.46 min MH+316.1；1H NMR(CDCl3)：9.56(1H，s)，8.11(2H，d，J8.7Hz)，7.98(1H，d，J1.9Hz)，7.55(1H，dd，J8.82.1Hz)，7.46-7.41(3H，m)，3.60(1H，q，J7.0Hz)，1.41(3H，d，J7.0Hz)
Method 3G (Compound II)
As in method 3C, except that the acid chloride is replaced with the corresponding anhydride.
2, 2, 2-trifluoro-N- (2-p-tolylbenzo [ d ] oxazol-5-yl) acetamide
LCMS RT ═ 6.93 min, MH+321.0；1H NMR(DMSO)：11.46(1H，br)，8.22(2H，d，J8.6Hz)，8.15(1H，d，J1.9Hz)，7.85(1H，d，J8.8Hz)，7.73-7.68(3H，m)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -2, 2, 2-trifluoroacetamide
LCMS RT 7.12 min, MH+340.8；1H NMR(DMSO)：11.43(1H，br)，8.12-8.09(3H，m)，7.82(1H，d，J8.8Hz)，7.67(1H，dd，J8.92.1Hz)，7.45(2H，d，J8.0Hz)
Method 3H (Compound II)
3-morpholino-N- (2-phenylbenzo [ d ] oxazol-5-yl) propanamide
A2M solution of trimethylaluminum in toluene (0.22mL, 0.43mmol) was added to 2-phenylbenzo [ d ] dissolved in toluene (2.5mL)]Oxazol-5-amine (75mg, 0.36mmol) and 3-morpholinopropionic acidMethyl ester (63. mu.L, 0.39 mmol). The resulting solution was heated twice in a microwave at 160 ℃ for 5 minutes. After cooling, sodium bicarbonate solution was added and the aqueous layer was extracted with ethyl acetate. The organic layer was then washed with brine and over anhydrous MgSO4The combined organic layers were dried. After evaporation, the impurities were removed by filtration through a silica plug, eluting with ethyl acetate/hexane-50: 50v/v and methanol to give the desired product, to give the title compound 17.5mg (14%) (LCMS RT-5.54 UIm)5MH+352.0)。
1H NMR(DMSO)：10.25(1H，s)，8.22-8.15(3H，m)，7.73(1H，d，J8.8Hz)，7.65-7.59(3H，m)，7.52(1H，dd，J8.82.0Hz)，3.60-3.57(4H，m)，2.68-2.64(2H，m)，2.44-2.41(4H，m)
Method 4 (Compound III)
N- (2-phenylbenzo [ d ] oxazol-5-yl) propane-1-sulfonamide
To 2-phenylbenzo [ d ] at room temperature]To a solution of oxazol-5-amine (100mg, 0.48mmol) in dichloromethane (2ml) was added pyridine (83 μ L, 0.95mmol) followed by propane-1-sulfonyl chloride (61 μ L, 0.52 mmol). The resulting solution was then stirred at room temperature for 16 hours. Dichloromethane was added and the organic layer was washed with saturated copper sulfate solution. Over anhydrous MgSO4The combined organic layers were dried and evaporated. The insoluble solid obtained is then treated with saturated NaHCO3Aqueous washes gave the title compound 37.2mg (25%) (lcmrsrt ═ 6.25 min, MH+317.0)。
1H NMR(DMSO)：9.89(1H，br)，8.21-8.18(2H，m)，7.77(1H，d，J8.8Hz)，7.66-7.59(4H，m)，7.28(1H，dd，J8.82.1Hz)，3.10-3.04(2H，m)，1.77-1.64(2H，m)，0.94(3H，t，J7.5Hz)
The following compounds were prepared by the same general procedure and purified by column chromatography eluting with ethyl acetate, hexane-30: 70 v/v.
N- (2-phenylbenzo [ d ] oxazol-5-yl) propane-2-sulfonamide
LCMS RT ═ 6.16 min, MH+317.0；1H NMR(DMSO)：9.89(1H，br)，8.21-8.18(2H，m)，7.76(1H，d，J8.8Hz)，7.69-7.59(4H，m)，7.30(1H，dd，J8.82.2Hz)，1.26(6H，d，J6.9Hz)
N- (2-phenylbenzo [ d ] oxazol-5-yl) benzenesulfonamides
LCMS RT ═ 6.43 minutes, MH+350.8；1H NMR(DMSO)：10.40(1H，br)，8.15(2H，dd，J7.21.6Hz)，7.77-7.74(2H，m)，7.68-7.51(7H，m)，7.46(1H，d，J2.1Hz)，7.12(1H，dd，J8.82.1Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) propane-1-sulfonamide
LCMS RT ═ 6.53 min, MH+331.0；1H NMR(DMSO)：9.85(1H，br)，8.80(2H，d，J7.8Hz)，7.74(1H，d，J9.0Hz)，7.60(1H，d，J2.0Hz)，7.44(2H，d，J8.1Hz)，7.26(1H，dd，J8.72.2Hz)，3.09-3.04(2H，m)，2.42(3H，s)，1.74-1.64(2H，m)，0.94(3H，t，J7.6Hz)
N- (2-p-tolylbenzo [ d ] oxazol-5-yl) propane-2-sulfonamide
LCMS RT 6.58 min MH+330.9；1H NMR(DMSO)：9.85(1H，br)，8.08(2H，d，J8.2Hz)，7.72(1H，d，J8.6Hz)，7.62(1H，d，J1.8Hz)，7.43(2H，d，J8.2Hz)，7.28(1H，dd，J8.82.2Hz)，2.60-2.57(1H，m)，2.42(3H，s)，1.26(6H，d，J6.8Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) propane-1-sulfonamide
LCMS RT ═ 6.81 minutes, MH+350.9；1H NMR(DMSO)：9.73(1H，br)，8.20(2H，d，J8.7Hz)，7.77(1H，d，J8.6Hz)，7.71(2H，d，J8.7Hz)，7.63(1H，d，J1.9Hz)，7.29(1H，dd，J8.82.2Hz)，3.10-3.05(2H，m)，1.77-1.65(2H，m)，0.94(3H，t，J7.6Hz)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) propane-2-sulfonamide
LCMS RT ═ 6.68 min, MH+351.0；1H NMR(DMSO)：9.88(1H，br)，8.19(2H，d，J8.7Hz)，7.76(1H，d，J8.8Hz)，7.70(2H，d，J8.7Hz)，7.65(1H，d，J2.0Hz)，7.32(1H，dd，J8.82.2Hz)，3.24(1H，t，J6.7Hz)，1.26(6H，d，J6.7Hz)
Method 5 (Compound IV)
N- (pyridin-4-ylmethyl) -2-p-tolylbenzo [ d ] oxazol-5-amine
To 2-p-tolylbenzo [ d ] dissolved in 1, 2-dichloroethane (20mL) at room temperature]Oxazol-5-amine (500mg, 2.32mmol) was added to acetic acid (142 μ L, 2.32mmol) and isonicotinaldehyde (222.5 μ L, 2.29mmol) and the mixture stirred for 1 hour. Sodium triacetoxyborohydride (707mg, 3.35mmol) was then added, and the mixture was stirred at room temperature for 24 hours. The mixture was then diluted with dichloromethane and the organic layer was NaHCO3And (5) washing with saturated aqueous solution. Over anhydrous MgSO4The combined organic layers were dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate: hexane ═ 20:80 to give the title compound 328mg (47%) (LCMS RT ═ 6.27 min, MH+316.1)
1H NMR(DMSO)：8.50(2H，d，J6.0Hz)，8.00(2H，d，J8.1Hz)，7.48-7.37(5H，m)，6.76-6.72(2H，m)，6.51(1H，t，J6.2Hz)，4.38(2H，d，J6.1Hz)，2.39(3H，s)
The following compounds were prepared using the same general procedure.
N-benzyl-2-phenylbenzo [ d ] oxazol-5-amines
LCMS RT 7.90 min MH+301.0；1H NMR(DMSO)：9.14-8.10(2H，m)，7.61-7.56(3H，m)，7.48-7.21(6H，m)，6.79-6.75(2H，m)，6.39(1H，t，J6.0Hz)，4.32(2H，d，J6.1Hz)
N-butyl-2-phenylbenzo [ d ] oxazol-5-amines
LCMS RT＝8.25 minutes, MH+267.0；1H NMR(DMSO)：8.16-8.12(2H，m)，7.61-7.58(3H，m)，7.47(1H，d，J8.7Hz)，6.81(1H，d，J2.1Hz)，6.72(1H，dd，J8.82.3Hz)，6.64(1H，t，J5.5Hz)，3.08-3.00(2H，m)，1.64-1.51(2H，m)，1.49-1.35(2H，m)，0.94(3H，t，J7.2Hz)
N-isobutyl-2-phenylbenzo [ d ] oxazol-5-amines
LCMS RT 8.26 min MH+267.0；1H NMR(DMSO)：8.15-8.12(2H，m)，7.62-7.51(3H，m)，7.46(1H，d，J8.8Hz)，6.81(1H，d，J2.1Hz)，6.74(1H，dd，J8.82.3Hz)，5.73(1H，t，J5.6Hz)，2.87(2H，t，J6.1Hz)，1.95-1.82(1H，m)，0.97(6H，d，J6.6Hz)
N-butyl-2- (4-chlorophenyl) benzo [ d ] oxazol-5-amine
LCMS RT ═ 9.58 min, MH+301.1；1H NMR(DMSO)：8.14(2H，d，J8.7Hz)，7.66(2H，d，J8.7Hz)，7.47(1H，d，J8.7Hz)，6.81(1H，d，J2.1Hz)，6.73(1H，dd，J8.82.2Hz)，6.67(1H，t，J5.7Hz)，3.07-3.00(2H，m)，1.62-1.53(2H，m)，1.48-1.36(2H，m)，0.94(3H，t，J7.2Hz)
2- (4-chlorophenyl) -N-isobutylbenzo [ d ] oxazol-5-amine
LCMS RT 8.85 min, MH+301.0；1H NMR(DMSO)：8.14(2H，d，J8.7Hz)，7.66(2H，d，J8.7Hz)，7.47(1H，d，J8.8Hz)，6.80(1H，d，J2.0Hz)，6.75(1H，dd，J8.82.2Hz)，5.75(1H，t，J5.7Hz)，2.87(2H，d，J6.2Hz)，1.93-1.82(1H，m)，0.97(6H，d，J6.7Hz)
N-benzyl-2- (4-chlorophenyl) benzo [ d ] oxazol-5-amine
LCMS RT 8.39 min MH+335.0；1H NMR(DMSO)：8.11(2H，d，J8.8Hz)，7.65(2H，d，J8.7Hz)，7.47(1H，d，J9.4Hz)，7.42-7.21(5H，m)，6.81-6.78(2H，m)，6.42(1H，t，J5.8Hz)，4.32(2H，d，J6.8Hz)
N-butyl-2-p-tolylbenzo [ d ] oxazol-5-amine
LCMS RT 8.44 min MH+281.0；1H NMR(DMSO)：8.02(2H，d，J8.2Hz)，7.46-7.38(3H，m)，6.79(1H，d，J2.0Hz)，6.69(1H，dd，J8.82.4Hz)，5.62(1H，t，J5.7Hz)，3.06-3.00(2H，m)，2.40(3H，s)，1.62-1.53(2H，m)，1.48-1.36(2H，m)，0.94(3H，t，J7.2Hz)
N-isobutyl-2-p-tolylbenzo [ d ] oxazol-5-amine
LCMS RT 8.48 min MH+281.0；1H NMR(DMSO)：8.03(2H，d，J8.1Hz)，7.45-7.38(3H，m)，6.79(1H，d，J2.1Hz)，6.71(1H，dd，J8.82.3Hz)，5.70(1H，t，J5.7Hz)，2.86(2H，t，J6.3Hz)，2.40(3H，s)，1.95-1.81(1H，m)，0.97(6H，d，J6.7Hz)
N-benzyl-2-p-tolylbenzo [ d ] oxazol-5-amine
LCMS RT 7.95 min MH+315.1；1H NMR(DMSO)：8.00(2H，d，J8.1Hz)，7.46-7.21(8H，m)，6.77-6.73(2H，m)，6.37(1H，t，J6.4Hz)，4.32(2H，d，J6.0Hz)，2.40(3H，s)
2- (4-chlorophenyl) -N, N-diisobutylbenzo [ d ] oxazol-5-amine
LCMS RT ═ 17.03 min, MH+357.1；1H NMR(DMSO)：8.26(2H，d，J8.5Hz)，7.80(2H，d，J8.6Hz)，7.67(1H，d，J9.0Hz)，7.09(1H，d，J2.3Hz)，6.96(1H，dd，J9.12.4Hz)，3.32(4H，d，J7.2Hz)，2.20-2.10(2H，m)，1.02(12H，d，J6.6Hz)
Method 6 (mixture V)
1-phenyl-3- (2-phenylbenzo [ d ] oxazol-5-yl) urea
2-Phenylbenzo [ d ] in dichloromethane (2mL) at room temperature]Oxazol-5-amine (75mg, 0.36mmol) was added to phenyl isocyanate (43 μ L, 0.39 mmol). The solution was stirred at room temperature for 16 hours. The precipitate obtained is filtered offWashing with dichloromethane afforded the title compound 99.9mg (85%) (lcmrsrt ═ 6.45 min, MH+330.1)
1H NMR(DMSO)：8.85(1H，s)，8.71(1H，s)，8.22-8.19(2H，m)，8.00(1H，d，J2.0Hz)，7.71(1H，d，J8.9Hz)，7.65-7.60(3H，m)，7.50-7.47(2H，m)，7.40(1H，dd，J8.82.1Hz)，7.30(2H，t，J8.4Hz)，7.02-6.95(1H，m)
The following compounds were prepared using the same general procedure.
1-isopropyl-3- (2-phenylbenzo [ d ] oxazol-5-yl) urea
LCMS RT 5.94 min MH+296.0；1H NMR(DMSO)：8.47(1H，s)，8.20-8.16(2H，m)，7.93(1H，d，J1.9Hz)，7.64-7.59(4H，m)，7.30(1H，dd，J8.82.1Hz)，6.03(1H，d，J7.5Hz)，3.85-3.74(1H，m)，1.12(6H，d，J6.5Hz)
Method 7 (Compound VI)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -N-methylpropanamide
To sodium hydride (15mg, 0.37mmol) was slowly added N- (2- (4-chlorophenyl) benzo [ d ] under nitrogen at 0 deg.C]Oxazol-5-yl) propionamide (100mg, 0.33mmol) in dimethylformamide (10 mL). After 10 minutes at 0 deg.C, methyl iodide (56 μ L, 0.37mmol) was added and the solution was allowed to return to room temperature for 16 hours. The mixture was diluted with ethyl acetate and then washed three times with water. Over anhydrous MgSO4The combined organic layers were dried and evaporated. The solid obtained is purified by column chromatography, purified with ethyl acetate: hexane 50:50 elution gave the title compound 36.4mg (35%) (lcmrsrt 7.00 min, MH+315.0)
1H NMR(CDCl3)：8.13(2H，d，J8.6Hz)，7.55-7.52(2H，m)，7.46(2H，d，J8.6Hz)，7.13(1H，dd，J8.32.0Hz)，3.26(3H，s)，2.04(2H，q，J7.6Hz)，1.00(3H，t，J7.6Hz)
Method 7 (Compound VIb)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -N-methylisobutylamide
LCMS RT 7.44 min MH+329.1；1H NMR(DMSO)：8.22(2H，d，J8.7Hz)，7.91-7.87(2H，m)，7.72(2H，d，J8.6Hz)，7.43(1H，d，J8.3Hz)，3.20(3H，s)，2.46-2.42(1H，m)，0.93(6H，d，J6.6Hz)
2- (4-chlorophenyl) -N-isobutyl-N-methylbenzo [ d ] oxazol-5-amine
LCMS RT ═ 10.59 min, MH+315.1；1H NMR(DMSO)：8.15(2H，d，J8.6Hz)，7.67(2H，d，J8.6Hz)，7.56(1H，d，J9.0Hz)，6.96(1H，d，J2.5Hz)，6.84(1H，dd，J9.12.5Hz)，3.17(2H，d，J7.3Hz)，2.97(3H，s)，2.13-1.97(1H，m)，0.90(6H，d，J6.7Hz)
Method 8 (Compound VII)
N- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) -2-methylpropanethioamide
N- (2- (4-chlorophenyl) benzo [ d ] in toluene (2mL) at 110 deg.C]Oxazol-5-yl) isobutyramide (50mg, 0.16mmol) was added to Lawesson's reagent (35mg, 0.09 mmol). The resulting solution was heated at 110 ℃ for 7 hours. After cooling, the solution was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine and then over anhydrous MgSO4Dried and evaporated. The solid obtained is purified by column chromatography, purified with ethyl acetate: hexane-20: 80v/v elution gave the title compound 13.8mg (26%) (LCMS RT-7.36 min, MH+331.2)
1H NMR(DMSO)：11.59(1H，s)，8.37(1H，d，J2.0Hz)，8.22(2H，d，J8.8Hz)，7.83(1H，d，J8.7Hz)，7.73-7.65(3H，m)，3.18-3.09(1H，m)，1.25(6H，d，J6.7Hz)
Method 9 (Compound VIII)
2- (4-chlorophenyl) benzo [ d ] oxazole-5-diazotetrafluoroborate
To an aqueous solution (3mL) of 2- (4-chlorophenyl) benzo [ d ] oxazol-5-amine (500mg, 2.04mmol) and tetrafluoroboric acid (50% aqueous solution, 2mL) was added an aqueous solution (2mL) of sodium nitrite (140mg, 2.04mmol) at 0 ℃ and added dropwise over 5 minutes. The resulting mixture was stirred at 0 ℃ for 15 minutes and then at room temperature for 1 hour. The solid was filtered off and washed with dilute aqueous tetrafluoroborate and methanol to give the title compound 370mg (53%), which was used without further characterization.
Method 10 (Compound IX)
S-2- (4-chlorophenyl) benzo [ d ] oxazol-5-ylethylthiol ester
A solution of potassium thioacetate (130mg, 1.13mmol) in DMSO (2.8mL) was stirred at room temperature, and 2- (4-chlorophenyl) benzo [ d ] was added dropwise thereto]Oxazole-5-diazotetrafluoroborate (370mg, 1.08mmol) in DMSO (1.4 mL). After 15 minutes, the mixture was heated to 70 ℃ for 1 hour. After cooling, the mixture was diluted with water and then extracted several times with ethyl acetate. The combined organic layers were washed with brine and then over anhydrous MgSO4Dried and evaporated. The solid obtained is purified by column chromatography, using a gradient of ethyl acetate: hexane-5: 95v/v to 15:85v/v elution and trituration with diethyl ether/hexane afforded the title compound 11.3mg (3%) (LCMS RT-7.89 min, MH+304.2)
1HNMR(CDCl3)：8.24(2H，d，J8.7Hz)，7.88(1H，dd，J1.70.4Hz)，7.67(1H，dd，J8.70.4Hz)，7.57(2H，d，J8.8Hz)，7.46(1H，dd，J8.41.7Hz)，2.51(3H，s)
Method 11A (Compound X)
5- (ethylsulfonyl) -2- (5-methylthiophen-2-yl) benzo [ d ] oxazole
To a solution of 2-amino-4- (ethylsulfonyl) phenol (452.7mg, 2.25mmol) in ethanol (17mL) was added 5-methyl-2-thiophenecarboxaldehyde (242 μ L, 2.25mmol) with stirring. The mixture was heated at 70 ℃ for 70 minutes. After cooling, a small amount of precipitate formed. After filtration and evaporation of the filtrate, the resulting product was dissolved in acetonitrile (9.8mL) and lead tetraacetate (887mg, 2 mmol). The resulting mixture was heated at 100 ℃ for 5 minutes. After cooling, the reaction mixture was filtered off and the filtrate was evaporated in vacuo. The resulting mixture was purified by column chromatography using ethyl acetate: hexane ═ 20:80v/v elution, followed by purification by reverse phase HPLC gave the title compound 2.2mg (0.3%) (LCMS RT ═ 6.41 min, MH+308.1)
1H NMR(DMSO)：8.22(1H，dd，J1.80.5Hz)，8.02(1H，dd，J8.60.5Hz)，7.92-7.88(2H，m)，7.08(1H，dd，J3.71.0Hz)，3.37(2H，q，J7.3Hz)，2.60(3H，d，J0.6Hz)，1.12(3H，t，J7.4Hz)
Method 11B (Compound X)
As in method 11A, but replacing lead tetraacetate with iodosamide diacetate.
5- (ethylsulfonyl) -2- (thiophen-2-yl) benzo [ d ] oxazole
LCMS RT ═ 6.08 min, MH+294.1；1H NMR(DMSO)：8.26(1H，d，J1.7Hz)，8.08-8.04(3H，m)，7.93(1H，dd，J8.51.8Hz)，7.36(1H，dd，J4.93.8Hz)，3.38(2H，q，J7.3Hz)，1.13(3H，t，J7.4Hz)
5- (ethylsulfonyl) -2- (3-methylthiophen-2-yl) benzo [ d ] oxazole
LCMS RT ═ 6.45 min, MH+308.1；1H NMR(DMSO)：8.02(1H，d，J1.80.5Hz)，7.81(1H，dd，J8.50.5Hz)，7.69-7.66(2H，m)，6.98(1H，dd，J5.00.4Hz)，3.15(2H，q，J7.3Hz)，2.47(3H，s)，0.88(3H，t，J7.4Hz)
5- (ethylsulfonyl) -2- (5-methylfuran-2-yl) benzo [ d ] oxazole
LCMS RT 5.53 min MH+292.1；1H NMR(DMSO)：8.00(1H，d，J1.80.6Hz)，7.81(1H，d，J6.6Hz)，7.69(1H，dd，J8.61.9Hz)，7.26(1H，d，J3.7Hz)，6.31-6.27(1H，m)，3.18-3.14(2H，m)，2.24(3H，s)，0.90(3H，t，J7.4Hz)
5- (ethylsulfonyl) -2- (4-methylthiophen-2-yl) benzo [ d ] oxazole
LCMS RT ═ 6.40 min, MH+616.9；1H NMR(DMSO)：8.24(1H，d，J1.80.5Hz)，8.03(1H，dd，J8.60.5Hz)，7.94-7.89(2H，m)，7.65(1H，t，J1.2Hz)，3.42-3.36(2H，m)，2.32(3H，d，J0.6Hz)，1.12(3H，t，J7.5Hz)
Method 12 (Compound XI)
N-butyl-2-p-tolylbenzo [ d ] oxazole-5-carboxamide
2-p-tolylbenzo [ d ] in anhydrous dimethylformamide (10mL)]Oxazole-5-carboxylic acid (100mg, 0.39mmol) was added to HATU (165mg, 0.44mmol) and diisopropylethylamine (206. mu.L, 1.18 mmol). The mixture was stirred at room temperature for 10 minutes. Then butan-1-amine (43 μ L, 0.44mmol) was added and the resulting mixture was stirred at room temperature for 16 h. Ethyl acetate was added and the organic layer was washed 3 times with water. The combined organic layers were dried over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography using ethyl acetate/hexane-40: elution at 60v/v gave the title compound 26mg (11%) (LCMS RT ═ 6.81 min, MH+309.1)。
1H NMR(CDCl3)：8.22-8.15(3H，m)，7.89(1H，dd，J8.11.1Hz)，7.67(1H，d，J8.3Hz)，7.40(2H，d，J7.5Hz)，6.17(1H，br)，3.59-3.52(2H，m)，2.51(3H，s)，1.72-1.64(2H，m)，1.54-1.46(2H，m)，1.03(3H，t，J7.3Hz)
The following compounds were prepared using the same general procedure.
N-propyl-2-p-tolylbenzo [ d ] oxazole-5-carboxamide
LCMS RT ═ 6.42 min, MH+295.1；1H NMR(CDCl3)：8.08(2H，d，J8.2Hz)，8.04(1H，d，J1.4Hz)，7.77(1H，dd，J8.51.7Hz)，7.54(1H，d，J8.6Hz)，7.28(2H，d，J7.9Hz)，6.07(1H，br)，3.44-3.37(2H，m)，2.39(3H，s)，1.65-1.55(2H，m)，0.95(3H，t，J7.5Hz)
N-isopropyl-2-p-tolylbenzo [ d ] oxazole-5-carboxamide
LCMS RT ═ 6.38 min, MH+295.1；1H NMR(CDCl3)：8.20(2H，d，J8.2Hz)，8.15(1H，d，J1.4Hz)，7.87(1H，dd，J8.51.8Hz)，7.65(1H，d，J8.5Hz)，7.40(2H，d，J8.0Hz)，6.00(1H，br)，4.43-4.31(1H，m)，2.51(3H，s)，1.35(6H，d，J6.6Hz)
2-p-tolylbenzo [ d ] oxazole-5-carboxamide
LCMS RT 5.61 min MH+253.0；1H NMR(DMSO)：8.30(1H，d，J1.2Hz)，8.12(2H，d，J8.2Hz)，7.98(1H，dd，J8.51.7Hz)，7.81(1H，d，J8.5Hz)，7.45(2H，d，J8.0Hz)，2.44(3H，s)
2- (4-chlorophenyl) -N-isopropylbenzo [ d ] oxazole-5-carboxamide
LCMS RT ═ 6.68 min, MH+315.5；1H NMR(DMSO)：8.36-8.31(2H，m)，8.23(2H，d，J8.7Hz)，7.98(1H，dd，J8.51.7Hz)，7.87(1H，d，J8.5Hz)，7.72(2H，d，J8.7Hz)，4.19-4.08(1H，m)，1.21(6H，d，J6.6Hz)
2- (4-chlorophenyl) benzo [ d ] oxazole-5-carboxamide
LCMS RT 5.81 min MH+273.2；1H NMR(DMSO)：8.11(1H，s)，8.01(2H，d，J8.3Hz)，7.89(1H，br)，7.78(1H，d，J8.6Hz)，7.64(1H，d，J8.6Hz)，7.49(2H，d，J8.3Hz)，7.25(1H，br)
Method 8 (Compound iso-VI)
2- (4-chlorophenyl) -N-methylbenzo [ d ] oxazole-5-carboxamide
LCMS RT ═ 6.09 minutes, MH+286.9；1H NMR(DMSO)：8.57(1H，br)，8.28(1H，d，J1.2Hz)，8.23(2H，d，J8.7Hz)，7.96(1H，dd，J8.61.7Hz)，7.87(1H，d，J8.6Hz)，7.72(2H，d，J8.6Hz)，2.83(3H，d，J4.5Hz)
2- (4-chlorophenyl) -N-isopropyl-N-methylbenzo [ d ] oxazole-5-carboxamide
LCMS RT ═ 6.90 min, MH+329.0；1H NMR(DMSO)：8.23(2H，d，J8.6Hz)，7.88-7.81(2H，m)，7.72(2H，d，J8.7Hz)，7.44(1H，d，J8.2Hz)，2.88-2.78(3H，m)，1.18-1.12(6H，m)
Method 7 (Compound iso-VII)
2- (4-chlorophenyl) -N-isopropylbenzo [ d ] oxazole-5-thiocarboxamide
LCMS RT 7.37 min MH+331.0；1H NMR(DMSO)：10.18(1H，d，J7.3Hz)，8.23(2H，d，J8.8Hz)，8.11(1H，dd，J1.70.5Hz)，7.88(1H，dd，J8.61.8Hz)，7.83(1H，dd，J8.8Hz)
Process 13 (Compound XII)
5- (4-methoxyphenyl) -2-p-tolylbenzo [ d ] oxazole
To 5-bromo-2-p-tolylbenzo [ d]To a solution of oxazole (146.1mg, 0.50mmol) in dioxane (1.5mL) was added water (0.5mL), 4-methoxyphenylboronic acid (114mg, 0.75mmol), potassium carbonate (138mg, 1.00mmol) and tetrakis (triphenyl)Phenylphosphine) palladium (0) (3 mg). The resulting suspension was heated at 150 ℃ for 15 minutes with a microwave. After cooling, the reaction was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography using ethyl acetate/hexane ═ 1: 99v/v elution gave the title compound 60mg (38%) (LCMS RT ═ 9.18 min, MH+316.1)。
1H NMR(DMSO)：8.12(2H，d，J8.2Hz)，7.99(1H，d，J1.5Hz)，7.82(1H，d，J8.5Hz)，7.71-7.64(3H，m)，7.45(2H，d，J8.0Hz)，7.06(2H，d，J8.8Hz)，3.82(3H，s)，2.43(3H，s)
The following compounds were prepared using the same general procedure.
N- (4- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) phenyl) acetamide
LCMS RT 7.51 min MH+362.8；1H NMR(DMSO)：10.04(1H，s)，8.23(2H，d，J8.5Hz)，8.05(1H，d，J1.6Hz)，7.86(1H，d，J8.5Hz)，7.73-7.69(7H，m)，2.09(3H，s)
2- (4-chlorophenyl) -5- (4- (ethylsulfonyl) phenyl) benzo [ d ] oxazole
LCMS RT 8.31 min MH+397.8；1H NMR(DMSO)：8.27-8.23(3H，m)，8.09-7.94(5H，m)，7.85(1H，dd，J8.61.8Hz)，7.73(2H，d，J8.7Hz)，3.39-3.34(2H，m)，1.16(3H，t，J7.5Hz)
Methyl 4- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) benzoate
LCMS RT ═ 9.34 min, MH+363.9；1H NMR(DMSO)：8.25(2H，d，J8.7Hz)，8.20(1H，d，J1.3Hz)，8.08(2H，d，J8.6Hz)，7.95-7.91(3H，m)，7.83(1H，dd，J8.61.8Hz)，7.73(2H，d，J8.7Hz)，3.90(3H，s)
N- (3- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) phenyl) acetamide
LCMS RT 7.40 min, MH+363.0；1H NMR(DMSO)：10.05(1H，s)，8.25(2H，d，J8.7Hz)，8.00(1H，d，J1.4Hz)，7.98-7.95(1H，m)，7.90(1H，d，J8.5Hz)，7.72(2H，d，J8.8Hz)，7.67(1H，dd，J8.51.8Hz)，7.60-7.57(1H，m)，7.42-7.40(2H，m)，2.09(3H，s)
2- (4-chlorophenyl) -5- (4-morpholinylphenyl) benzo [ d ] oxazole
LCMS RT 17.49 min MH+391.0；1HNMR(DMSO)：8.23(2H，d，J8.9Hz)，8.00(1H，d，J1.4Hz)，7.83(1H，d，J8.6Hz)，7.74-7.67(3H，m)，7.64(2H，d，J8.9Hz)，7.06(2H，d，J8.9Hz)，3.79-3.75(4H，m)，3.19-3.15(4H，m)
2- (4-chlorophenyl) -5- (3- (ethylthio) phenyl) benzo [ d ] oxazole
LCMS RT ═ 10.82 min, MH+365.7；1HNMR(DMSO)：8.25(2H，d，J8.7Hz)，8.11(1H，d，J1.4Hz)，7.89(1H，d，J8.6Hz)，7.77-7.70(3H，m)，7.62(1H，t，J1.7Hz)，7.55(1H，dt，J7.61.2Hz)，7.44(1H，t，J7.6Hz)，7.35-7.32(1H，m)，3.09(2H，q，J7.3Hz)，1.29(3H，t，J7.4Hz)
N- (2- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) phenyl) acetamide
LCMS RT ═ 6.84 min, MH+363.0；1H NMR(DMSO)：9.29(1H，s)，8.24(2H，d，J8.6Hz)，7.86(1H，d，J8.4Hz)，7.78-7.76(1H，m)，7.72(2H，d，J8.5Hz)，7.53-7.29(5H，m)，1.87(3H，s)
2- (4-chlorophenyl) -5- (4-methoxypyridin-3-yl) benzo [ d ] oxazole
LCMS RT 7.46 min MH+337.0；1H NMR(DMSO)：8.49(1H，d，J5.8Hz)，8.45(1H，s)，8.24(2H，d，J8.9Hz)，7.95(1H，d，J1.70.5Hz)，7.87(1H，dd，J8.50.6Hz)，7.72(2H，d，J8.8Hz)，7.58(1H，dd，J8.51.7Hz)，7.21(1H，d，J5.8Hz)，3.89(3H，s)
2- (4-chlorophenyl) -5- (6-methoxypyridin-3-yl) benzo [ d ] oxazole
LCMS RT 8.83 min, MH+337.0；1HNMR(DMSO)：8.57(1H，dd，J2.60.6Hz)，8.24(2H，d，J8.8Hz)，8.13-8.10(2H，m)，7.89(1H，dd，J8.60.5Hz)，7.75-7.70(3H，m)，6.95(1H，dd，J8.60.6Hz)，3.92(3H，s)
3- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) benzoic acid
LCMS RT 4.62 min MH+350.1；1H NMR(DMSO)：8.27-8.23(3H，m)，8.12(1H，d，J1.4Hz)，8.03-7.95(2H，m)，7.91(1H，d，J8.7Hz)，7.78(1H，dd，J8.51.8Hz)，7.72(2H，d，J8.8Hz)，7.64(1H，t，J7.7Hz)
2- (4-chlorophenyl) -5- (6-chloropyridin-3-yl) benzo [ d ] oxazole
LCMS RT ═ 8.59 min, MH+340.9；1H NMR(DMSO)：8.33(1H，d，J2.2Hz)，8.28-8.23(4H，m)，7.95(1H，d，J8.6Hz)，7.83(1H，dd，J8.51.8Hz)，7.73(2H，d，J8.7Hz)，7.65(1H，d，J8.4Hz)
2- (4-chlorophenyl) -5- (6-fluoropyridin-3-yl) benzo [ d ] oxazole
LCMS RT 8.05 min, MH+325.0；1H NMR(DMSO)：8.65(1H，d，J2.7Hz)，8.39(1H，td，J8.22.7Hz)，8.25(2H，d，J8.7Hz)，8.20(1H，dd，J1.80.5Hz)，7.94(1H，dd，J8.60.6Hz)，7.80(1H，dd，J8.61.9Hz)，7.73(2H，d，J8.7Hz)，7.33(1H，dd，J8.63.0Hz)
2- (4-chlorophenyl) -5- (6-morpholinopyridin-3-yl) benzo [ d ] oxazole
LCMS RT 8.46 min MH+391.8；1H NMR(DMSO)：8.55(1H，d，J2.4Hz)，8.23(2H，d，J8.7Hz)，8.06(1H，d，J1.4Hz)，7.98(1H，dd，J8.92.6Hz)，7.86(1H，d，J8.8Hz)，7.73-7.69(3H，m)，6.96(1H，d，J8.9Hz)，3.75-3.71(4H，m)，3.53-3.49(4H，m)
2- (4-chlorophenyl) -5- (6-methoxypyridin-2-yl) benzo [ d ] oxazole
LCMS RT ═ 9.84 min, MH+337.1；1H NMR(DMSO)：8.54(1H，d，J1.6Hz)，8.26-8.23(3H，m)，7.91(1H，d，J8.7Hz)，7.82(1H，t，J7.9Hz)，7.74-7.68(3H，m)，6.81(1H，d，J8.1Hz)，4.00(3H，s)
3- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) aniline
LCMS RT 7.78 min, MH+321.1；1H NMR(DMSO)：8.24(2H，d，J8.7Hz)，7.73(1H，dd，J1.80.4Hz)，7.85(1H，d，J8.5Hz)，7.72(2H，d，J8.8Hz)，7.63(1H，dd，J8.61.8Hz)，7.13(1H，t，J7.8Hz)，6.90(1H，t，J1.9Hz)，6.87-6.82(1H，m)，6.62-6.57(1H，m)，5.19(2H，s)
4- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) aniline
LCMS RT 7.77 min, MH+321.1；1H NMR(DMSO)：8.22(2H，d，J8.7Hz)，7.91(1H，d，J1.5Hz)，7.78(1H，d，J8.6Hz)，7.71(2H，d，J8.6Hz)，7.61(1H，dd，J8.61.8Hz)，7.43(2H，d，J8.6Hz)，6.67(2H，d，J8.6Hz)，5.26(2H，s)
5- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) pyridinyl-2-amines
LCMS RT 7.12 min, MH+322.1；1H NMR(DMSO)：8.32(1H，d，J2.2Hz)，8.23(2H，d，J8.7Hz)，7.98(1H，d，J1.4Hz)，7.84-7.77(2H，m)，7.72(2H，d，J8.7Hz)，7.64(1H，dd，J8.51.8Hz)，6.56(1H，d，J8.6Hz)，6.09(2H，s)
4- (5- (4-chlorophenyl) benzo [ d ] oxazol-2-yl) aniline
LCMS RT 7.73 min, MH+320.9；1H NMR(DMSO)：7.94(1H，d，J1.5Hz)，7.89(2H，d，J8.6Hz)，7.78-7.74(3H，m)，7.60(1H，dd，J8.61.8Hz)，7.53(2H，d，J8.6Hz)，6.71(2H，d，J8.7Hz)，6.04(2H，s)
Method 13a (Compound XIIa)
N- (5- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) pyridin-2-yl) acetamide
To 5- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) pyridinyl-2-amine (96.5mg, 0.30mmol) in anhydrous pyridine (3mL) was added acetyl chloride (26 μ L, 0.36mmol) at room temperature and stirred at 80 ℃ for 40 h. After cooling, the mixture was poured into water to give a precipitate, which was filtered. The resulting solid was purified by column chromatography using ethyl acetate/hexane-20: 80v/v to yield 45mg (41%) of the title compound.
1H NMR(DMSO)：10.61(1H，s)，8.73-8.71(1H，m)，8.24(2H，d，J8.6Hz)，8.18-8.16(3H，m)，7.91(1H，d，J8.5Hz)，7.79(1H，dd，J8.61.8Hz)，7.73(2H，d，J8.6Hz)，2.13(3H，s)
Method 13b (Compound XIIb)
Ethyl phosphinic acid methyl ester
A solution of methanol (2.70mL, 66.75mmol) and triethylamine (4.23mL, 30.35mmol) in diethyl ether (15mL) was added dropwise to a solution of ethyl dichlorophosphite (3.15mL, 30.35mmol) in diethyl ether (30mL) at 0 ℃ according to a known method (cf. Xu, Y. et al, Synthesis, 1984, 778-780). After the addition was complete, the resulting slurry was refluxed for 1 hour. After cooling at 0 ℃, the precipitated solid was filtered off and washed with diethyl ether. The filtrate was then concentrated to give a colorless oil, which was taken to the next step without purification.
2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl (ethyl) phosphite methyl ester
5-bromo-2-p-tolylbenzo [ d ] in anhydrous toluene (10mL)]To oxazole (519.7mg, 1.68mmol) and methyl ethylphosphite (276.9mg, 2.02mmol) were added tetrakis (triphenylphosphine) palladium (0) (101.6mg) and triethylamine (7.5mL, 5.4 mmol). The resulting suspension was refluxed for 18 hours under nitrogen atmosphere. After cooling, ethyl acetate was added and the organic layer was washed with water. MergingIn anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography, eluting with a gradient (starting with hexane/ethyl acetate followed by methanol/ethyl acetate 5:95v/v) and then purified by reverse phase HPLC to give the title compound 10.4mg (2%) (LCMS RT ═ 6.32 min, MH+336.1)。
1H NMR(DMSO)：8.24(2H，d，J8.7Hz)，8.18-8.13(1H，m)，8.00(1H，ddd，J8.52.40.6Hz)，7.81(1H，ddd，J10.98.21.4Hz)，7.73(2H，d，J8.7Hz)，3.54(3H，d，J10.9Hz)，2.09-1.94(2H，m)，1.04-0.91(3H，m)
Method 14 (Compound XIII)
N- (4- (5-chlorobenzo [ d ] oxazol-2-yl) phenyl) acetamide
To 4- (5-chlorobenzo [ d ] at room temperature]To a solution of oxazol-2-yl) aniline (122.3mg, 0.50mmol) in pyridine (3mL) was added acetyl chloride (39. mu.L, 0.55 mmol). The resulting compound was stirred at room temperature for 16 hours. The solution was then poured into water and the resulting precipitate was collected by filtration. Washing with diluted hydrochloric acid solution and then with water gave the title compound 120mg (84%) (LCMS RT ═ 6.38 min, MH+287.0)。
1H NMR(DMSO)：10.33(1H，s)，8.14(2H，d，J8.7Hz)，7.88-7.80(4H，m)，7.45(1H，dd，J8.72.1Hz)，2.11(3H，s)
The following compounds were prepared using the same general procedure.
N- (4- (5-chlorobenzo [ d ] oxazol-2-yl) phenyl) isobutyramide
LCMS RT 7.03 min, MH+315.1；1H NMR(DMSO)：10.22(1H，s)，8.14(2H，d，J8.7Hz)，7.88-7.79(4H，m)，7.45(1H，dd，J8.72.1Hz)，2.70-2.61(1H，m)，1.13(6H，d，J6.8Hz)
N- (4- (5-chlorobenzo [ d ] oxazol-2-yl) phenyl) thiophene-2-carboxamide
LCMS RT 7.44 min MH+355.0；1H NMR(DMSO)：10.57(1H，s)，8.21(2H，d，J8.9Hz)，8.09(1H，dd，J3.81.1Hz)，8.02(2H，d，J8.9Hz)，7.93-7.90(2H，m)，7.82(1H，d，J8.6Hz)，7.46(1H，dd，J8.62.1Hz)，7.27(1H，dd，J4.93.8Hz)
N- (4- (6-chlorobenzo [ d ] oxazol-2-yl) phenyl) acetamide
LCMS RT ═ 6.37 minutes, MH+287.0；1HNMR(DMSO)：10.32(1H，s)，8.13(2H，d，J8.8Hz)，7.96(1H，d，J1.8Hz)，7.84-7.77(3H，m)，7.45(1H，dd，J8.41.9Hz)，2.11(3H，s)
N- (4- (6-chlorobenzo [ d ] oxazol-2-yl) phenyl) isobutyramide
LCMS RT 7.18 min MH+315.1；1H NMR(DMSO)：10.22(1H，s)，8.12(2H，d，J8.8Hz)，7.96(1H，d，J1.8Hz)，7.86(2H，d，J8.9Hz)，7.79(1H，d，J8.5Hz)，7.45(1H，dd，J8.52.0Hz)，2.70-2.61(1H，m)，1.13(6H，d，J6.9Hz)
N- (4- (6-chlorobenzo [ d ] oxazol-2-yl) phenyl) thiophene-2-carboxamide
LCMS RT 7.61 min MH+354.9；1HNMR(DMSO)：10.57(1H，s)，8.19(2H，d，J8.9Hz)，8.09(1H，dd，J3.71.0Hz)，8.01(2H，d，J8.9Hz)，7.98(1H，d，J1.8Hz)，7.92(1H，dd，J5.01.0Hz)，7.81(1H，d，J8.5Hz)，7.46(1H，dd，J8.52.0Hz)，7.26(1H，dd，J5.03.8Hz)
N- (4- (5-bromobenzo [ d ] oxazol-2-yl) phenyl) acetamide
1H NMR(DMSO)：10.35(1H，s)，8.14(2H，d，J8.8Hz)，8.01(1H，d，J1.8Hz)，7.83(2H，d，J8.7Hz)，7.76(1H，d，J8.6Hz)，7.57(1H，dd，J8.62.0Hz)，2.11(3H，s)
N- (4- (5- (4-chlorophenyl) benzo [ d ] oxazol-2-yl) phenyl) acetamide
LCMS RT 7.53 min MH+363.0；1H NMR(DMSO)：10.34(1H，s)，8.17(2H，d，J8.7Hz)，8.06-8.04(1H，m)，7.87-7.82(3H，m)，7.78(2H，d，J8.5Hz)，1.12-1.61(1H，m)，7.55(2H，d，J8.6Hz)，2.12(3H，s)
N- (4- (5, 6-dimethylbenzo [ d ] oxazol-2-yl) -3-hydroxyphenyl) acetamide
LCMS RT 7.22 min MH+297.2；1HNMR(DMSO)：11.24(1H，br)，10.24(1H，s)，7.91(1H，d，J8.6Hz)，7.59(2H，d，J6.4Hz)，7.51(1H，d，J1.9Hz)，7.22(1H，dd，J8.72.0Hz)，2.37(3H，s)，2.34(3H，s)，2.09(3H，s)
Method 15 (Compound XIV)
1- (2- (4-chlorophenyl) benzo [ d ] oxazol-5-yl) ethanol
To 1- (2- (4-chlorophenyl) benzo [ d ] at 0 DEG C]To a solution of oxazol-5-yl) ethanone (150mg, 0.55mmol) in tetrahydrofuran was added sodium borohydride (52mg, 1.38 mmol). The resulting compound was stirred at room temperature for 16 hours. The reaction was quenched with 1M hydrochloric acid solution at 0 ℃ and extracted three times with ethyl acetate. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography and eluted with a gradient (ethyl acetate/hexane ═ 1:3v/v to ethyl acetate/hexane ═ 1:2v/v) to give the title compound 81.7mg (54%) (LCMS RT ═ 6.47 min, MH+274.0)。
1H NMR(DMSO)：8.20(2H，d，J8.7Hz)，7.76-7.68(4H，m)，7.44(1H，dd，J8.61.6Hz)，5.31(1H，d，J4.3Hz)，4.92-4.83(1H，m)，1.38(3H，d，J6.4Hz)
2- (3 ', 4 ' -dichlorophenyl) -5- (l ' -hydroxyethyl) -benzoxazole
LCMS RT 7.18 min MH+308.1；1HNMR(DMSO)：8.36(1H，d，J2.0Hz)，8.16(1H，dd，J8.52.0Hz)，7.90(1H，d，J8.4Hz)，7.78-7.77(1H，m)，7.74(1H，d，J8.4Hz)，7.47(1H，dd，J8.61.7Hz)，5.32(1H，d，J4.3Hz)，4.93-4.84(1H，m)，1.39(3H.d，J6.4Hz)
5-nitrobenzo [ d ] oxazole-2 (3H) -thiones
A suspension of 2-amino-4-nitrophenol (1.54g, 10mmol) and O-ethyldithiopotassium carbonate (1.68g, 10.5mmol) in dry pyridine (10mL) was stirred at 120 ℃ for 16 h and then held at room temperature for 16 h according to a well-known method (cf. Batista-Parra, A. et al, Heterocycles, 2003, 60, 1367). The solution was poured into water and then a hydrochloric acid solution was added. The resulting precipitate was collected by filtration, washed with dilute aqueous hydrochloric acid, then with water, and dried in a vacuum oven to give the title compound 3.3g (84%).
1H NMR(DMSO)：8.18(1H，dd，J8.92.4Hz)，7.94(1H，dd，J2.40.4Hz)，7.73(1H，dd，J8.90.4Hz)
Method 16 (Compound XV)
2-morpholino-5-nitrobenzo [ d ] oxazoles
5-Nitrobenzo [ d ] in tetrahydrofuran (3mL)]Oxazole-2 (3H) -thione (98.1mg, 0.5mmol) and morpholine (66 μ L, 0.75mmol) were heated in a microwave at 150 ℃ for 15 minutes. After cooling, the mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and over anhydrous MgSO4Dried and absorbed on silica. Purification by column chromatography eluting with ethyl acetate/hexane 25:75v/v gave the title compound 115mg (92%).
1H NMR(DMSO)：8.10(1H，d，J2.3Hz)，8.00(1H，dd，J8.82.4Hz)，7.66(1H，d，J8.8Hz)，3.76-3.72(4H，m)，3.67-3.64(4H，m)
Method 17a (Compound XVI)
2-morpholinobenzo [ d ] oxazol-5-amines
2-morpholine-5-nitrobenzo [ d ]]A solution of oxazole (130mg, 0.52mmol) in ethanol/water 1:1v/v (10mL) was treated with sodium dithionite (182mg, 1.04mmol) at room temperature and then refluxed for 16 hours. After cooling, the mixture was diluted with water and extracted with ethyl acetate. Over anhydrous MgSO4The organic layer was dried and evaporated to give the title compound 35mg (30%).
1H NMR(DMSO)：7.03(1H，d，J8.5Hz)，6.50(1H，d，J2.1Hz)，6.25(1H，dd，J8.42.2Hz)，4.80(2H，s)，3.71-3.68(4H，m)，3.53-3.50(4H，m)
Method 17b (Compound XVI)
N-2- (4-chlorophenylmethyl) benzo [ d ] oxazole-2, 5-diamine
To N- (4-chlorophenylmethyl) -5-nitrobenzo [ d ] at 90 deg.C]To a suspension of oxazolyl-2-amine (150mg, 0.50mmol) in ethanol/water 1:1v/v (10mL) was added ammonium chloride (53mg, 1.0mmol) followed by iron powder (140mg, 2.5 mmol). The resulting mixture was stirred at 90 ℃ for 4 hours. After cooling, ethyl acetate was added and the solution was passed throughA pad. The organic layer was then washed with brine and over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography using ethyl acetate/hexane ═ 50: elution at 50v/v gave the title compound 60mg (44%) (LCMS RT ═ 5.60 min, MH+274.0)。
1H NMR(DMSO)：8.20(1H，t，J6.2Hz)，7.42-7.36(4H，m)，6.97(1H，d，J8.4Hz)，6.45(1H，d，J2.1Hz)，6.20(1H，dd，J8.42.2Hz)，4.72(2H，s)，4.46(2H，d，J6.2Hz)
Method 18 (Compound XVII)
2- (4-chlorobenzylthio) -5-nitrobenzo [ d ] oxazoles
To 5-nitrobenzo [ d]To a suspension of oxazole-2 (3H) -thione (196.2mg, 1.0mmol) in chloroform (10mL) was added triethylamine (278. mu.L, 2mmol) followed by 1- (bromomethyl) -4-chlorobenzene (226mg, 1.1 mmol). The reaction was stirred at 60 ℃ for 2 hours. After cooling, the reaction was diluted with ethyl acetate and washed with brine and aqueous hydrochloric acid. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes ═ 1:10v/v to give the title compound 250mg (78%) (LCMS RT ═ 7.64 min)
1H NMR(DMSO)：8.52(1H，d，J2.3Hz)，8.27(1H，dd，J8.92.3Hz)，7.92(1H，d，J9.0Hz)，7.58(2H，d，J8.5Hz)，7.42(2H，d，J8.5Hz)，4.67(2H，s)
Method 19 (Compound XVIII)
2- (4-chlorobenzylthio) benzo [ d ] oxazol-5-amine
To 2- (4-chlorobenzylthio) -5-nitrobenzo [ d ] at 90 deg.C]Oxazole (220mg, 0.70mmol) was added to a suspension of ethanol/water (5mL/5mL) ammonium chloride (75mg, 1.4mmol) followed by iron powder (192mg, 3.44 mmol). The resulting mixture was stirred at 90 ℃ for 4 hours. After cooling, ethyl acetate was added and the solution was passed throughA pad. The organic layer was then washed with brine and over anhydrous MgSO4Dried and evaporated to give the title compound 190mg (94%) (LCMS RT ═ 6.54 min, MH+290.9)。
1H NMR(DMSO)：7.52(2H，d，J8.7Hz)，7.40(2H，d，J8.5Hz)，7.26(1H，d，J8.7Hz)，6.74(1H，d，J1.9Hz)，6.54(1H，dd，J8.72.2Hz)，5.06(2H，s)，4.55(2H，s)
Method 20 (Compound XIX)
N- (2- (4-chlorophenylmethylthio) benzo [ d ] oxazol-5-yl) acetamide
To 2- (4-chlorobenzylthio) benzo [ d ] ne at room temperature]A solution of oxazol-5-amine (87mg, 0.30mmol) in anhydrous pyridine (3mL) was added acetyl chloride (21. mu.L, 0.30 mmol). The resulting solution was stirred at room temperature for 16 hours. Then, water was added, and the precipitate was collected by filtration, washed with a diluted hydrochloric acid aqueous solution, and then washed with water. Trituration with diethyl ether afforded the title compound 40mg (40%) (LCMS RT ═ 6.40 min, MH+333.1)
1HNMR(DMSO)：10.08(1H，s)，8.01(1H，d，J1.8Hz)，7.58-7.52(3H，m)，7.43-7.35(3H，m)，4.60(2H，s)，2.06(3H，s)
The following compounds were prepared using the same general procedure described above.
N- (2- (4-chlorobenzylthio) benzo [ d ] oxazol-5-yl) isobutyramide
LCMS RT 7.00 min, MH+361.1；1H NMR(DMSO)：9.96(1H，s)，8.04(1H，d，J1.8Hz)，7.58-7.52(3H，m)，7.43-7.39(3H，m)，4.60(2H，s)，2.65-2.60(1H，m)，1.12(6H，d，J6.8Hz)
Method 21 (Compound XX)
2-chloro-5-nitrobenzo [ d ] oxazoles
To a solution of 5-nitrobenzo [ d ] oxazole-2 (3H) -thione (2.52g, 12.86mmol) in phosphorus oxychloride (21mL) was added phosphorus pentachloride (2.68g, 12.86 mmol). The mixture was then heated to 100 ℃ for 2.5 hours. After cooling, the excess phosphorus oxychloride was removed in vacuo and the resulting mixture was used without working up without identification.
Method 22 (Compound XXI)
5-nitro-2- (thien-2-yl) benzo [ d ] oxazoles
2-chloro-5-nitrobenzo [ d ] in dioxane (12.2mL) under nitrogen]A mixture of oxazole (404mg, 2.04mmol), 2- (tributylstannyl) -thiophene (648. mu.L, 2.04mmol) and tetrakis (triphenylphosphine) palladium (0) (40.8mg) was heated at 100 ℃ for 16 h. Adding ethyl acetate, washing the organic layer with water, and purifying with anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexane 10:90v/v and then purified by reverse phase HPLC to give the title compound 3mg (2%) (LCMS RT 6.95 min).
1HNMR(DMSO)：8.54(1H，d，J2.2Hz)，8.27(1H，dd，J9.02.3Hz)，8.04(1H，dd，J5.41.2Hz)，7.93(1H，d，J9.0Hz)，7.69(1H，dd，J3.71.2Hz)，7.29(1H，dd，J5.43.7Hz)
Method 23 (Compound XXII)
5-amino-2- (5, 6-dimethyl-1H-benzo [ d ] imidazol-2-yl) phenol
To polyphosphoric acid was added 4, 5-dimethylbenzene-1, 2-diamine (500mg, 3.67mmol) and 4-amino-2-hydroxybenzoic acid (562mg, 3.67mmol) at 130 ℃ and the resulting mixture was heated to 130 ℃ for 16 hours. The solution was poured into water and the resulting precipitate was dissolved in ethyl acetate and taken up with Na2CO3And (5) cleaning. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes-50: 50v/v to give the title compound 260mg (28%) (LCMS RT-6.14 min, MH+254.1)。
1H NMR(DMSO)：13.07(1H，s)，12.40(1H，s)，7.61(1H，d，J8.3Hz)，7.35(1H，s)，7.24(1H，s)，6.19(1H，dd，J8.52.2Hz)，6.12(1H，d，J2.1Hz)，5.59(2H，s)，2.32(3H，s)，2.30(3H，s)
The following compounds were prepared using the same general procedure.
2- (3-methyl-4-nitrophenyl) -1H-benzo [ d ] imidazole
LCMS RT 5.87 min MH+254.1；1HNMR(DMSO)：13.20(1H，br)，9.31(1H，s)，8.21-8.19(2H，m)，7.67-7.64(2H，m)，7.28-7.25(2H，m)，2.65(3H，s)
2- (6-nitro-1H-benzo [ d ] imidazol-2-yl) phenol
LCMS RT 6.48 min MH+256.0；1H NMR(DMSO)：13.50(1H，br)，12.40(1H，br)，8.56(1H，s)，8.20-8.14(2H，m)，7.84(1H，d，J8.8Hz)，7.48-7.43(1H，m)，7.12-7.04(2H，m)
2- (4-chlorophenyl) -6-nitro-1H-benzo [ d ] imidazole
LCMS RT ═ 6.24 min, MH+273.9；1H NMR(DMSO)：13.80(1H，br)，8.54(1H，d，J2.1Hz)，8.29(2H，d，J8.6Hz)，8.21(1H，dd，J8.92.2Hz)，7.84(1H，d，J8.9Hz)，7.75(2H，d，J8.5Hz)
Method 24 (Compound XXIIb)
2- (5-amino-1H-benzo [ d ] imidazol-2-yl) phenol
To 2- (5-nitro-1H-benzo [ d ] in ethyl acetate/water/acetic acid ═ 1:1:0.01v/v/v (10mL)]Imidazol-2-yl) phenol (90mg, 0.35mmol) was added palladium on charcoal (15 mg). The reaction vessel was purged three times with nitrogen, followed by three times with hydrogen, and then shaken in hydrogen for 2 hours. In the filtrate by washing with ethyl acetateBefore the pad, the reaction vessel was finally purged three times with nitrogen. The organic layer was washed with saturated NaHCO3And (4) washing with an aqueous solution. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes ═ 2:1v/v to give the title compound 60mg (76%) (LCMS RT ═ 5.39 min, MH+226.1)
1H NMR(DMSO)：13.28(1H，br)，12.63(1H，br)，7.72(1H，d，J8.4Hz)，7.33-7.28(2H，m)，6.99-6.94(2H，m)，6.71-6.58(2H，m)，5.12(2H，s)
Method 25 (Compound XXIII)
N- (2-p-tolyl-1H-benzo [ d ] imidazolyl-5-yl) butanamide
To 2-p-tolyl-1H-benzo [ d ] at room temperature]A solution of imidazolyl-5-amine (150mg, 0.67mmol) in pyridine (10mL) was added butyl chloride (77 μ L, 0.74 mmol). The resulting mixture was stirred at room temperature for 16 hours. Ethyl acetate was added and the organic layer was washed twice with saturated aqueous copper sulfate solution, followed by sodium bicarbonate and brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes-50: 50v/v to give the title compound 56mg (28%) (LCMS RT-6.96 min, MH+294.0)
1H NMR(DMSO)：12.68(1H，br)，9.87(1H，s)，8.08-8.00(3H，m)，7.52-7.20(4H，m)，2.38(3H，s)，2.31(2H，t，J7.3Hz)，1.70-1.58(2H，m)，0.94(3H，t，J7.4Hz)
The following compounds were prepared using the same general procedure.
N- (2-p-tolyl-1H-benzo [ d ] imidazol-5-yl) isobutyramide
LCMS RT 5.43 min MH+294.1；1H NMR(DMSO)：12.67(1H，br)，9.91(1H，s)，8.08-8.01(3H，m)，7.50-7.28(4H，m)，4.03(1H，q，J7.2Hz)，2.38(3H，s)，1.13(6H，d，J6.8Hz)
N- (2- (4-chlorophenyl) -1H-benzo [ d ] imidazolyl-5-yl) butanamide
LCMS RT 5.54 min MH+314.0；1H NMR(DMSO)：12.85(1H，br)，9.90(1H，s)，8.14(3H，d，J8.6Hz)，7.62(2H，d，J8.7Hz)，7.53(1H，br)，7.25(1H，br)，2.32(2H，t，J7.1Hz)，1.71-1.58(2H，m)，0.94(3H，t，J7.5Hz)
N- (2-phenyl-1H-benzo [ d ] imidazolyl-5-yl) isobutyramide
LCMS RT 5.32 min MH+280.0；1H NMR(DMSO)：12.80(1H，br)，9.85(1H，s)，8.16-8.09(3H，m)，7.58-7.47(4H，m)，7.28(1H，d，J8.1Hz)，2.68-2.60(1H，m)，1.13(6H，d，J6.9Hz)
N- (2-phenyl-1H-benzo [ d ] imidazolyl-5-yl) butanamide
LCMS RT 5.32 min MH+280.0；1H NMR(DMSO)：12.77(1H，br)，9.90(1H，s)，8.15-8.12(3H，m)，7.58-7.45(4H，m)，7.26(1H，br)，2.31(2H，t，J7.1Hz)，1.71-1.58(2H，m)，0.94(3H，t，J7.5Hz)
N- (2- (4-chlorophenyl) -1H-benzo [ d ] imidazolyl-5-yl) isobutyramide
LCMS RT 5.71 min MH+314.0；1H NMR(DMSO)：12.89(1H，br)，9.86(1H，s)，8.18-8.10(3H，m)，7.62(2H，d，J8.8Hz)，7.52(1H，d，J8.8Hz)，7.29(1H，d，J8.3Hz)，2.66-2.60(1H，m)，1.13(6H，d，J6.9Hz)
Method 26 (Compound XXIV)
2-amino-4-nitrobenzenethiol
2-fluoro-5-nitroaniline (1g, 6.41mmol), sodium sulfide nonahydrate (1.7g, 7.05mmol), sodium bicarbonate (600mg, 7.05mmol) and water (15mL) were combined and heated in a microwave at 125 ℃ for 5 minutes. After cooling, dichloromethane was added and the organic layer was washed with 2M aqueous brine solution and brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated to give the title compound 1.1g (33%).
1H NMR(DMSO)：7.61-7.55(2H，m)，7.47(1H，d，J8.2Hz)，7.31(3H，s)
Method 27 (Compound XXV)
2- (2-chlorophenyl) -5-nitrobenzo [ d ] thiazole
2-amino-4-nitrobenzenethiol (315mg, 1.85mmol), 2-chlorobenzoic acid (290mg, 1.85mmol) and Eaton's reagent (5mL) were combined and heated in a microwave at 130 ℃ for 10 minutes. After cooling, the mixture was poured into water, basified with 5M aqueous sodium hydroxide solution to give a precipitate, which was filtered off to give the title compound 530mg (98%).
1H NMR(DMSO)：8.93(1H，d，J2.2Hz)，8.53(1H，d，J8.9Hz)，8.37(1H，dd，J8.92.2Hz)，8.29(1H，dd，J7.41.9Hz)，7.78-7.75(1H，m)，7.70-7.60(2H，m)
Method 28 (Compound XXVI)
N- (2-chloro-5-nitrophenyl) -4-methylbenzamide
To 2-chloro-5-nitroaniline (2g, 11.59mmol) in pyridine (5mL) was added 4-methylbenzoyl chloride (1.6mL, 12.17mmol) at room temperature, followed by pyridine (5 mL). The mixture was stirred at room temperature for 16 hours. Then, ethyl acetate was added to the solution to obtain a precipitate, and the precipitate was filtered off, washed twice with ethyl acetate and then with hexane. Then washed with aqueous sodium bicarbonate, 1M aqueous sodium hydroxide, water and hexane to give the title compound (1.4g, 42%).
1H NMR(DMSO)：10.26(1H，s)，8.58(1H，d，J2.8Hz)，8.11(1H，dd，J8.92.8Hz)，7.93(2H，d，J8.2Hz)，7.87(1H，d，J8.9Hz)，7.38(2H，d，J8.0Hz)，2.41(3H，s)
Method 29 (Compound XXV)
5-nitro-2-p-tolylbenzo [ d ] thiazole
Sodium sulfide nonahydrate (875mg, 3.78mmol) and sulfur (120mg, 3.78mmol) were heated to melting. The water was removed by nitrogen to give a solid. The resulting solid was added to N- (2-chloro-5-nitrophenyl) -4-methylbenzamide (1g, 3.44mmol) in ethanol (20mL) at 85 ℃. The solution was stirred at 85 ℃ for 3 hours. After cooling, 2M aqueous HCl was added and the solution was extracted three times with ethyl acetate. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography, eluting with ethyl acetate/hexane 10:90v/v, to give the title compound 400mg (43%).
1H NMR(DMSO)：8.81(1H，d，J2.2Hz)，8.45(1H，d，J8.8Hz)，8.29(1H，dd，J8.82.3Hz)，8.06(2H，d，J8.2Hz)，7.44(2H，d，J8.0Hz)，2.42(3H，s)
Method 30 (Compound XXVII)
2-p-tolylbenzo [ d ] thiazol-5-amine
Reacting 5-nitro-2-p-tolylbenzo [ d]Thiazole (400mg, 1.48mmol) was suspended in ethanol/water (8mL/4mL) and heated at 80 ℃. To the suspension were added ammonium chloride (160mg, 2.96mmol) and iron powder (414mg, 7.40mmol), and the remaining mixture was stirred at 80 ℃ for 75 minutes. After cooling, the solution is passedThe pad was washed with ethanol. Water was added to the filtrate, ethanol was evaporated, and the remaining aqueous layer was extracted with ethyl acetate. The combined organic layers were over anhydrous MgSO4Dried and evaporated to give the title compound 220mg (62%) (LCMS RT ═ 6.51 min, MH+241.0)
1H NMR(DMSO)：7.91(2H，d，J8.1Hz)，7.68(1H，d，J8.6Hz)，7.35(2H，d，J8.0Hz)，7.15(1H，d，J2.0Hz)，6.77(1H，dd，J8.62.0Hz)，5.32(2H，s)，2.39(3H，s)
The following compounds were prepared using the same general procedure.
2-phenylbenzo [ d ] thiazol-5-amine
LCMS RT ═ 6.11 minutes, MH+227.1；1H NMR(DMSO)：8.04-8.01(2H，m)，7.71(1H，d，J8.5Hz)，7.56-7.53(3H，m)，7.18(1H，d，J2.1Hz)，6.79(1H，dd，J8.62.3Hz)，5.33(2H，s)
2- (4-chlorophenyl) benzo [ d ] thiazol-5-amine
LCMS RT ═ 6.72 min, MH+260.7；1H NMR(DMSO)：8.04(2H，d，J8.7Hz)，7.72(1H，d，J8.6Hz)，7.61(2H，d，J8.7Hz)，7.17(1H，d，J2.0Hz)，6.80(1H，dd，J8.62.2Hz)，5.35(2H，s)
2- (2-chlorophenyl) benzo [ d ] thiazol-5-amine
LCMS RT ═ 6.49 min, MH+260.8；1H NMR(DMSO)：8.19-8.16(1H，m)，7.76(1H，d，J8.6Hz)，7.69-7.66(1H，m)，7.56-7.52(2H，m)，7.22(1H，d，J2.0Hz)，6.85(1H，dd，J8.62.1Hz)，5.37(2H，s)
2- (3-chlorophenyl) benzo [ d ] thiazol-5-amine
LCMS RT ═ 6.79 min, MH+260.8；1H NMR(DMSO)：8.05-8.04(1H，m)，7.96(1H，dt，J7.01.7Hz)，7.74(1H，d，J8.6Hz)，7.64-7.55(2H，m)，7.19(1H，d，J1.7Hz)，6.82(1H，dd，J8.62.2Hz)，5.37(2H，s)
2- (3, 4-dichlorophenyl) benzo [ d ] thiazol-5-amine
LCMS RT 7.49 min MH+294.9；1H NMR(DMSO)：8.24(1H，d，J2.1Hz)，8.00(1H，dd，J8.42.1Hz)，7.82(1H，d，J8.4Hz)，7.76(1H，d，J8.6Hz)，7.20(1H，d，J1.9Hz)，6.84(1H，dd，J8.62.2Hz)，5.41(2H，s)
2- (2, 3-dichlorophenyl) benzo [ d ] thiazol-5-amine
LCMS RT 7.00 min, MH+294.9；1H NMR(DMSO)：8.08(1H，dd，J7.91.6Hz)，7.84(1H，dd，J8.01.6Hz)，7.78(1H，d，J8.6Hz)，7.55(1H，t，J8.0Hz)，7.22(1H，d，J2.0Hz)，6.87(1H，dd，J8.62.2Hz)，5.38(2H，s)
Method 31 (Compound XXVIII)
N- (2-p-tolylbenzo [ d ] thiazol-5-yl) butanamide
To 2-p-tolylbenzo [ d ] at room temperature]To a solution of thiazol-5-amine (110mg, 0.46mmol) in pyridine (3mL) was added butyl chloride (53. mu.L, 0.50 mmol). The resulting mixture was stirred at room temperature for 2 days. Ethyl acetate was added and the organic layer was washed with saturated aqueous copper sulfate solution, followed by aqueous sodium bicarbonate solution and finally brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate/hexanes-50: 50v/v to give the title compound 25mg (18%) (LCMS RT-7.10 min, MH+311.0)
1H NMR(DMSO)：10.12(1H，s)，8.43(1H，d，J1.8Hz)，8.02-7.96(3H，m)，7.58(1H，dd，J8.62.0Hz)，7.38(2H，d，J8.0Hz)，2.40(3H，s)，2.35(2H，t，J7.5Hz)，1.72-1.60(2H，m)，0.95(3H，t，J7.4Hz)
The following compounds were prepared using the same general procedure.
N- (2-p-tolylbenzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT 7.06 min MH+311.0；1H NMR(DMSO)：10.08(1H，s)，8.44(1H，d，J1.3Hz)，8.03-7.96(3H，m)，7.60(1H，dd，J8.71.6Hz)，7.38(2H，d，J8.0Hz)，2.69-2.60(1H，m)，2.40(3H，s)，1.15(6H，d，J6.8Hz)
N- (2-phenylbenzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT 6.56 min MH+297.0；1H NMR(DMSO)：10.07(1H，s)，8.47(1H，d，J1.8Hz)，8.11-8.07(2H，m)，8.04(1H，d，J8.6Hz)，7.64-7.56(4H，m)，2.70-2.61(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (4-chlorophenyl) benzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT 7.42 min MH+331.0；1H NMR(DMSO)：10.08(1H，s)，8.47(1H，d，J1.9Hz)，8.10(2H，d，J8.6Hz)，8.05(1H，d，J8.7Hz)，7.67-7.61(3H，m)，2.70-2.60(1H，m)，1.15(6H，d，J6.8Hz)
N- (2- (2-chlorophenyl) benzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT ═ 6.99 min, MH+330.9；1H NMR(DMSO)：10.12(1H，s)，8.55(1H，d，J1.9Hz)，8.25-8.22(1H，m)，8.10(1H，d，J8.8Hz)，7.74-7.55(4H，m)，2.72-2.63(1H，m)，1.17(6H，d，J6.8Hz)
N- (2- (3-chlorophenyl) benzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT 7.34 min MH+330.9；1H NMR(DMSO)：10.11(1H，s)，8.50(1H，d，J1.7Hz)，8.13-8.03(3H，m)，7.69-7.60(3H，m)，2.71-2.62(1H，m)，1.17(6H，d，J6.8Hz)
N- (2- (3, 4-dichlorophenyl) benzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT 8.21 min, MH+364.7；1H NMR(DMSO)：10.11(1H，s)，8.52-8.50(1H，m)，8.30(1H，d，J2.1Hz)，8.10-8.04(2H，m)，7.85(1H，d，J8.4Hz)，7.69-7.64(1H，m)，2.71-2.64(1H，m)，1.17(6H，d，J6.8Hz)
N- (2- (2, 3-dichlorophenyl) benzo [ d ] thiazol-5-yl) isobutyramide
LCMS RT 7.62 min MH+364.9；1H NMR(DMSO)：10.12(1H，s)，8.55(1H，d，J1.7Hz)，8.14-8.10(2H，m)，7.88(1H，dd，J8.01.4Hz)，7.67(1H，dd，J8.82.0Hz)，7.58(1H，t，J8.0Hz)，2.70-2.61(1H，m)，1.15(6H，d，J6.8Hz)
Method 32 (Compound XXIX)
4-chloro-N- (4- (methylthio) phenyl) benzamide
To 4- (methylthio) aniline (1mL, 8.19mmol) in dichloromethane (20mL) was added pyridine (2mL, 24.6 mmol). The resulting solution was cooled to 10-15 deg.C and 4-chlorobenzoyl chloride (1.14mL, 9.00mmol) was added over 5 minutes. The mixture was stirred at room temperature for 90 minutes. The precipitate was filtered off, washed with dichloromethane, 1M aqueous sodium hydroxide solution and 1M aqueous brine solution to give the title compound 2.12g (93%).
1H NMR(DMSO)：10.31(1H，s)，7.98(2H，d，J8.7Hz)，7.73(2H，d，J8.8Hz)，7.61(2H，d，J8.8Hz)，7.28(2H，d，J8.8Hz)，2.47(3H，s)
Method 33 (Compound XXX)
4-chloro-N- (4- (methylthio) phenyl) benzothioamide
A suspension of 4-chloro-N- (4- (methylthio) phenyl) benzamide (1g, 3.60mmol) and Lawesson's reagent (875mg, 2.16mmol) in toluene (25mL) was heated to 110 ℃ for 16 hours. After cooling, the toluene was removed in vacuo and the resulting solid was purified by column chromatography eluting with a gradient (hexane to ethyl acetate/hexane-30: 70v/v) to give the title compound 503mg (48%).
LCMS RT ═ 6.98 min, MH+294.1；1H NMR(DMSO)：11.80(1H，s)，7.85(2H，d，J8.6Hz)，7.78(2H，d，J8.7Hz)，7.54(2H，d，J8.6Hz)，7.33(2H，d，J8.7Hz)
Method 34 (Compound XXXI)
2- (4-chlorophenyl) -6- (methylthio) benzo [ d ] thiazole
To an aqueous solution (5mL) of potassium (III) ferrocyanide (670mg, 2.04mmol) at 90 ℃ over 5 minutesA solution of 4-chloro-N- (4- (methylthio) phenyl) benzothioamide (150mg, 0.51mmol) in ethanol (2mL) and 3M aqueous sodium hydroxide (1.4mL, 4.08mmol) were added dropwise. The resulting mixture was heated at 90 ℃ for 30 minutes. After cooling, the precipitate formed was filtered off and washed with water to give a yellow solid. The solid was purified by column chromatography eluting with a gradient (hexane to ethyl acetate/hexane-5: 95v/v) to give the title compound 100mg (67%) (LCMS RT-9.37 min, MH+292.2)
1H NMR(DMSO)：8.11-8.06(3H，m)，7.98(1H，d，J8.6Hz)，7.65(2H，d，J8.7Hz)，7.45(1H，dd，J8.61.9Hz)，2.58(3H，s)
Method 35 (Compound XXXII)
2- (4-chlorophenyl) -6- (methylsulfonyl) benzo [ d ] thiazole
To 2- (4-chlorophenyl) -6- (methylthio) benzo [ d]To a solution of thiazole (240mg, 0.82mmol) in dichloromethane (20mL) was added 3-chloroperoxybenzoic acid (77% solution in water, 710mg, 4.11mmol) over a period of 5 minutes. The resulting mixture was stirred at room temperature for 3 hours. A1M aqueous solution of sodium hydroxide was carefully added, and the mixture was stirred for 5 minutes. The organic layer was then washed with 1M aqueous sodium hydroxide solution over anhydrous MgSO4Dried and evaporated. The resulting solid was recrystallized from hot ethyl acetate to give the title compound 125mg (47%) (LCMS RT ═ 6.81 min, MH+324.0)
1H NMR(CDCl3)：8.61(1H，dd，J1.80.4Hz)，8.26(1H，dd，J8.60.5Hz)，8.14-8.09(3H，m)，7.57(2H，d，J8.6Hz)，3.19(3H，s)
Method 36 (Compound XXXIII)
2- (4-chlorophenyl) -5-phenyl-1H-indole
To a suspension of 5-bromo-2- (4-chlorophenyl) -1H-indole (200mg, 0.65mmol) in dioxane/water ═ 4:1v/v (5mL) was added phenylboronic acid (87mg, 0.72mmol) and a few milligrams of tetrakis (triphenylphosphine) palladium (0). The resulting suspension was heated in a microwave at 160 ℃ for 15 minutes. After cooling, the reaction was poured into water to form a precipitate, which was filtered off and washed with water. The resulting solid was purified by column chromatography, washed with a gradient (hexane to ethyl acetate/hexane: 30:70v/v) and then recrystallized from hot ethyl acetate to give the title compound 21mg (11%) (LCMS RT: 8.54 min, MH+304.1)
1H NMR(DMSO)：11.68(1H，s)，7.91(2H，d，J8.6Hz)，7.81(1H，d，J1.1Hz)，7.70-7.66(2H，m)，7.55(2H，d，J8.6Hz)，7.50-7.41(4H，m)，7.33-7.28(1H，m)，7.01(1H，d，J1.2Hz)
The following compounds were prepared using the same general procedure.
N- (4- (2- (4-chlorophenyl) -1H-indol-5-yl) phenyl) acetamide
LCMS RT ═ 6.69 min, MH+361.0；1H NMR(DMSO)：11.64(1H，s)，9.98(1H，s)，7.91(2H，d，J8.6Hz)，7.77(1H，d，J1.0Hz)，7.68-7.60(4H，m)，7.54(2H，d，J8.6Hz)，7.46(1H，d，J8.3Hz)，7.41(1H，dd，J8.51.6Hz)，6.99(1H，d，J1.5Hz)，2.07(3H，s)
Method 37 (Compound XXXIV)
1-methyl-6-nitro-1H-indoles
To a solution of 6-nitro-1H-indole (100mg, 0.62mmol) and 18-crown-6 (180mg, 0.68mmol) in anhydrous tetrahydrofuran (2mL) was slowly added tert-butyl potassium oxide (76mg, 0.68mmol) followed by methyl iodide (42. mu.L, 0.68mmol) at room temperature. The solution was stirred at room temperature for 30 minutes. Removing in vacuumTetrahydrofuran. Ethyl acetate was added and the organic layer was washed with water followed by brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated to yield 91mg (84%) of the title compound.
1H NMR(CDCl3)：8.16(1H，d，J1.8Hz)，7.85(1H，dd，J8.71.9Hz)，7.49(1H，d，J8.7Hz)，7.19(1H，d，J3.1Hz)，6.43(1H，dd，J3.10.9Hz)，3.74(3H，s)
Method 38 (Compound XXXV)
1-methyl-1H-indol-6-amines
1-methyl-6-nitro-1H-indole (90mg, 0.51mmol), ammonium chloride (55mg, 1.02mmol) and iron powder (143mg, 2.55mmol) were suspended in ethanol/water (2mL/1mL) and heated at 70 ℃ for 2 hours. After cooling, the solution was usedThe pad was filtered and the pad was washed with ethanol. Ethyl acetate was added to the filtrate, and the organic layer was washed twice with water. The combined organic layers were over anhydrous MgSO4Dried and evaporated to yield 30mg (37%) of the title compound.
1H NMR(DMSO)：7.17(1H，d，J8.4Hz)，6.93(1H，d，J3.1Hz)，6.51-6.49(1H，m)，6.41(1H，dd，J8.31.9Hz)，6.16(1H，d，J3.1Hz)，4.76(2H，s)，3.60(3H，s)
Method 39 (Compound XXXVI)
N- (1-methyl-1H-indol-6-yl) isobutyramide
To a solution of 1-methyl-1H-indol-6-amine (45mg, 0.31mmol) in pyridine (2mL) was added isobutyl chloride (35. mu.L, 0.34mmol) at room temperature. The resulting mixture was stirred at room temperature for 16 hours. Ethyl acetate was added and the organic layer was washed three times with brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated to give 24.3mg (36%) of the title compound (LCMS RT ═ 5.73 min, MH)+217.2)
1H NMR(DMSO)：9.78(1H，s)，7.96(1H，m)，7.44(1H，d，J8.4Hz)，7.24(1H，d，J3.1Hz)，7.08(1H，dd，J8.41.7Hz)，6.35(1H，dd，J3.00.7Hz)，3.73(3H，s)，2.68-2.61(1H，m)，1.13(6H，d，J6.9Hz)
The following compounds were prepared using the same general procedure.
N- (1-benzyl-1H-indol-6-yl) isobutyramide
LCMS RT 6.36 min MH+293.2；1H NMR(DMSO)：9.73(1H，s)，7.90(1H，m)，7.45(1H，d，J8.5Hz)，7.41(1H，d，J3.1Hz)，7.34-7.24(3H，m)，7.14-7.10(3H，m)，6.42(1H，d，J3.2Hz)，5.35(2H，s)，1.08(6H，d，J6.8Hz)
Method 40 (Compound XXXVII)
N- (2-hydroxy-5-nitrophenyl) butanamide
Pyridine (10.5mL, 129.9mmol) was added to a solution of 2-amino-4-nitrophenol (10g, 64.9mmol) in dichloromethane (250mL) at 0 deg.C under nitrogen, followed by butyl chloride (7.05mL, 68.2mmol) over 5 minutes. After 30 minutes at 0 ℃, the solution was returned to room temperature for 2 days. The organic layer was washed with aqueous copper sulfate and brine. Insoluble material was filtered off from the aqueous layer and washed with water to give 4.95g (34%) of the title compound.
1H NMR(DMSO)：11.64(1H，br)，9.37(1H，s)，8.95(1H，d，J2.8Hz)，7.89(1H，dd，J8.92.8Hz)，7.02(1H，d，J8.9Hz)，2.43(2H，t，J7.4Hz)，1.67-1.55(2H，m)，0.92(3H，t，J7.5Hz)
Method 41 (Compound XXXVIII)
2-Butylamide-4-nitrobenzotrifluoride mesylate
To a solution of sodium hydride (220mg, 5.58mmol) in anhydrous acetonitrile (40mL) at 0 ℃ under a nitrogen atmosphere was added a solution of N- (2-hydroxy-5-nitrophenyl) butanamide (1g, 4.46mmol) in anhydrous acetonitrile (90 mL). The solution was then stirred at 0 ℃ for 30 minutes. Trifluoromethanesulfonic anhydride (825. mu.L, 4.90mmol) was added dropwise over 10 min at 0 ℃. After 3 hours at 0 ℃, the solution was stirred at room temperature for 3 hours. Water was added and the aqueous layer was extracted with ethyl acetate. The organic layer was then washed with dilute aqueous hydrochloric acid, aqueous sodium bicarbonate and brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting oil was stripped by column chromatography eluting with a gradient (hexane to ethyl acetate/hexane 25:75v/v) to give the title compound 860mg (54%).
1H NMR(CDCl3)：9.37(1H，d，J2.8Hz)，8.09(1H，dd，J9.12.8Hz)，7.53(2H，d，J9.1Hz)，2.50(2H，t，J7.6Hz)，1.91-1.78(2H，m)，1.09(3H，t，J7.5Hz)
Method 42 (Compound XXXIX)
N- (5-nitro-2- (phenylethynyl) phenyl) butanamide
To a solution of 2-butanamide-4-nitrophenyl trifluoromethanesulfonate (860mg, 2.42mmol) in anhydrous acetonitrile (30mL) under a nitrogen atmosphere were added tetrabutylammonium iodide (1.34g, 3.62mmol), tetrakis (triphenylphosphine) palladium (0) (280mg, 0.24mmol) and copper iodide (140mg, 0.72 mmol). Triethylamine (6mL) was then added followed by phenylacetylene (530. mu.L, 4.83 mmol). The resulting solution was stirred at room temperature for 2 hours. Then, ammonium chloride was added to terminate the reaction, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography, eluting with a gradient (hexanes to ethyl acetate) to give the title compound 580mg (78%).
1H NMR(DMSO)：9.81(1H，s)，8.74(1H，d，J2.3Hz)，8.01(1H，dd，J8.62.4Hz)，7.83(1H，d，J8.6Hz)，7.70-7.67(2H，m)，7.52-7.49(3H，m)，1.73-1.61(2H，m)，0.96(3H，t，J7.5Hz)
Method 43 (Compound XLa)
6-nitro-2-phenyl-1H-indoles
To a solution of N- (5-nitro-2- (phenylacetylene) phenyl) butanamide (580mg, 1.88mmol) in 1-methyl-2-pyrrolidone (20mL) under a nitrogen atmosphere was added potassium tert-butyloxide (243mg, 2.16 mmol). The resulting solution was heated at 70 ℃ for 6 hours and then held at room temperature for 16 hours. Water was added and the aqueous layer was extracted several times with ethyl acetate. The combined organic layers were washed 10 times with water, 3 times with brine, over anhydrous MgSO4Dried and evaporated. The resulting material was purified by column chromatography eluting with ethyl acetate/hexane 15:85v/v to give the title compound 175mg (39%).
1H NMR(DMSO)：12.35(1H，s)，8.30(1H，d，J2.1Hz)，7.97-7.90(3H，m)，7.73(1H，d，J8.9Hz)，7.57-7.52(2H，m)，7.47-7.42(1H，m)，7.17(1H，dd，J2.00.8Hz)
Method 44 (Compound XLb)
1-methyl-6-nitro-2-phenyl-1H-indoles
To a solution of 6-nitro-2-phenyl-1H-indole (106mg, 0.44mmol) and 18-crown-6 (130mg, 0.49mmol) in anhydrous tetrahydrofuran (2mL) was added tert-butyl potassium oxide (55mg, 0.49mmol) followed by methyl iodide (31. mu.L, 0.49mmol) at room temperature. The solution was stirred at room temperature for 30 minutes. The tetrahydrofuran was removed in vacuo. Ethyl acetate was added and the organic layer was washed with water and then brine. The combined organic layers were over anhydrous MgSO4Drying above and evaporation gave the title compound 110mg (98%).
1H NMR(DMSO)：8.60(1H，d，J2.1Hz)，8.03(1H，dd，J8.82.1Hz)，7.82(1H，d，J8.7Hz)，7.74-7.71(2H，m)，7.67-7.57(3H，m)，6.87(1H，d，J0.8Hz)，3.95(3H，s)
Method 45 (Compound XLI)
2-phenyl-1H-indol-6-amines
6-Nitro-2-phenyl-1H-indole (175mg, 0.73mmol), ammonium chloride (80mg, 1.47mmol) and iron powder (205mg, 3.68mmol) were suspended in ethanol/water (4mL/2mL) and heated at 70 ℃ for 2 hours. After cooling, the solution is passed throughThe pad was filtered and the pad was washed with ethanol. The organic layer was evaporated in vacuo to give a solid which was purified by column chromatography eluting with a gradient (ethyl acetate/hexane: 10:90v/v to ethyl acetate/hexane: 50v/v) to give the title compound 54mg (35%).
1H NMR(DMSO)：10.88(1H，s)，7.76-7.72(2H，m)，7.39(2H，t，J7.9Hz)，7.23-7.16(2H，m)，6.67(1H，dd，J2.00.7Hz)，6.59-6.57(1H，m)，6.39(1H，dd，J8.42.0Hz)，4.82(2H，s)
Method 46 (Compound XLII)
N- (2-phenyl-1H-indol-6-yl) isobutyramide
To a solution of 2-phenyl-1H-indol-6-amine (54mg, 0.26mmol) in pyridine (2mL) was added isobutyl chloride (30. mu.L, 0.29mmol) at room temperature. The resulting mixture was stirred at room temperature for 2 days. Upon addition of water, a precipitate formed. The solid was recrystallized from hot ethyl acetate to give the title compound 15mg (21%) (LCMS RT ═ 6.27 min, MH+279.0)
1H NMR(DMSO)：11.40(1H，s)，9.74(1H，s)，8.02(1H，s)，7.82(2H，d，J7.5Hz)，7.47-7.40(3H，m)，7.28(1H，t，J7.3Hz)，7.07(1H，dd，J8.51.6Hz)，6.83(1H，d，J1.1Hz)，2.67-2.60(1H，m)，1.13(6H，d，J6.7Hz)
The following compounds were prepared using the same general procedure.
N- (1-methyl-2-phenyl-1H-indol-6-yl) isobutyramide
LCMS RT ═ 6.66 min, MH+293.2；1H NMR(DMSO)：9.83(1H，s)，8.02(1H，s)，7.61-7.39(6H，m)，7.13(1H，dd，J8.51.7Hz)，6.50(1H，d，J0.5Hz)，3.69(3H，s)，2.69-2.60(1H，m)，1.13(6H，d，J6.8Hz)
Method 47 (Compound XLIIa)
5-nitro-2-phenylbenzofurans
An aqueous solution (6mL) of 2-iodo-4-nitrophenol (500mg, 1.89mmol), prolinol (573mg, 5.66mmol), palladium on charcoal (60mg, 0.06mmol), triphenylphosphine (59.4mg, 0.226mmol) and copper iodide (22mg, 0.113mmol) was stirred at room temperature for 1 hour. Ethynylbenzene (482mg, 4.72mmol) was added slowly and the resulting mixture was heated at 80 ℃ for 3 hours. After cooling, ethyl acetate was added and the mixture was passed throughA pad. Washing the filtrate with water; the combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting material was purified by column chromatography eluting with ethyl acetate/hexane-1: 40v/v to give the title compound 134mg (30%).
1H NMR(DMSO)：8.62(1H，d，J2.4Hz)，8.23(1H，dd，J9.12.5Hz)，8.00-7.96(2H，m)，7.89(1H，d，J9.0Hz)，7.66(1H，d，J0.4Hz)，7.60-7.46(3H，m)
Method 48 (Compound XLIIb)
2-phenylbenzofuranyl-5-amines
To 5-nitro-2-phenylbenzofuran (250mg, 1.04mmol) in ethanol/water 2:1v/v (12mL) was added ammonium chloride (112mg, 2.09mmol) and iron powder (292mg, 5.23mmol) at 80 ℃. The resulting mixture was heated at 80 ℃ for 4 hours. After cooling, the solution is passedThe pad was filtered and the pad was washed with ethanol. The organic layer was evaporated in vacuo to give a solid which was taken up in ethyl acetate and washed with water. The combined organic layers were over anhydrous MgSO4Drying above, and evaporation gave the title compound 211mg (96%).
1H NMR(DMSO)：7.87-7.83(2H，m)，7.50-7.44(2H，m)，7.40-7.34(1H，m)，7.28(1H，d，J8.7Hz)，7.20(1H，d，J0.7Hz)，6.74(1H，d，J2.2Hz)，6.60(1H，dd，J8.72.3Hz)，4.88(2H，s)
Method 49 (Compound XLIV)
N- (2-phenylbenzofuran-5-yl) isobutyramide
To a solution of 2-phenylbenzofuranyl-5-amine (210mg, 1.00mmol) in pyridine (5mL) was added butyl chloride (120. mu.L, 1.10mmol) at room temperature. The resulting mixture was then stirred at room temperature for 16 hours. Ethyl acetate was added, and the organic layer was washed with a saturated aqueous copper sulfate solution, followed by a saturated potassium carbonate solution. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting material was purified by column chromatography eluting with a gradient (ethyl acetate/hexane ═ 1:3v/v to ethyl acetate/hexane ═ 1:2v/v) to give the title compound 134mg (48%) (LCMS RT ═ 6.81 min, MH ═ m: (m ═ m: (m) —, m+280.1)。
1H NMR(DMSO)：9.87(1H，s)，8.05(1H，s)，7.91(2H，d，J7.4Hz)，7.58-7.48(3H，m)，7.45-7.38(3H，m)，2.66-2.54(1H，m)，1.13(6H，d，J6.8Hz)
The following compounds were prepared using the same general procedure.
2- (4' -chlorophenyl) -5-isobutyramide-benzofuran
LCMS RT 7.41 min MH+314.2；1H NMR(DMSO)：9.88(1H，s)，8.06(1H，d，J1.9Hz)，7.92(2H，d，J8.7Hz)，7.59-7.53(3H，m)，7.49(1H，d，J0.8Hz)，7.43(1H，dd，J9.02.2Hz)，2.66-2.56(1H，m)，1.13(6H，d，J6.8Hz)
Method 50 (Compound XLIV)
2-phenyl-5- (3 ', 3 ', 3 ' -trifluoropropionamide) benzofuran
To 3, 3, 3-trifluoropropionic acid (136mg, 1.06mmol) in dry dichloromethane (10mL) was added HATU (468mg, 1.23mmol) and diisopropylethylamine (580. mu.L, 3.35 mmol). The mixture was then stirred at room temperature for 10 minutes. 2-Phenylbenzofuranyl-5-amine (234mg, 1.12mmol) was then added and the resulting mixture was stirred at room temperature for 48 h. Ethyl acetate was added and the organic layer was washed once with saturated aqueous solution. The combined organic layers were over anhydrous MgSO4Dried and evaporated. The resulting solid was purified by column chromatography eluting with a gradient (ethyl acetate/hexanes ═ 1:3v/v to ethyl acetate/hexanes ═ 1:1v/v) followed by trituration in ethyl acetate to give the title compound 99.3mg (28%) (lcmrsrt ═ 6.62 min)
1H NMR(DMSO)：10.37(1H，s)，8.01(1H，d，J2.0Hz)，7.92(2H，dd，J7.51.5Hz)，7.61(1H，d，J8.8Hz)，7.55-7.41(4H，m)，7.38(1H，dd，J8.92.2Hz)，3.53(2H，q，J11.2Hz)
The compounds listed in table 2 may be prepared by methods similar to those described above, or by methods well known to those of ordinary skill in the art or in the literature.
Claims (3)
1. A compound or pharmaceutically acceptable salt thereof, wherein the compound is 5- (ethylsulfonyl) -2- (naphthalen-2-yl) benzo [ d ] oxazole.
2. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.
3. Use of a compound of claim 1, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating or preventing duchenne muscular dystrophy or becker muscular dystrophy.
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0602768.4 | 2006-02-10 | ||
| GB0602768A GB0602768D0 (en) | 2006-02-10 | 2006-02-10 | Treatment of muscular dystrophy |
| GB0614690.6 | 2006-07-24 | ||
| GB0614690A GB0614690D0 (en) | 2006-07-24 | 2006-07-24 | Method of treatment of duchenne muscular dystrophy |
| GB0619281.9 | 2006-09-29 | ||
| GB0619281A GB0619281D0 (en) | 2006-09-29 | 2006-09-29 | Treatment of duchenne muscular dystrophy |
| GB0623983A GB0623983D0 (en) | 2006-11-30 | 2006-11-30 | Treatment of duchenne muscular dystrophy |
| GB0623983.4 | 2006-11-30 | ||
| PCT/GB2007/050055 WO2007091106A2 (en) | 2006-02-10 | 2007-02-09 | Treatment of duchenne muscular dystrophy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1125577A1 HK1125577A1 (en) | 2009-08-14 |
| HK1125577B true HK1125577B (en) | 2012-09-14 |
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