CN102603750A - Synthesis method of triazolylquinoxalinone derivatives - Google Patents
Synthesis method of triazolylquinoxalinone derivatives Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 239000003446 ligand Substances 0.000 claims abstract description 9
- 238000010523 cascade reaction Methods 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 61
- 238000000034 method Methods 0.000 claims description 37
- -1 OR ' Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims description 6
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 229930182821 L-proline Natural products 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 229960002429 proline Drugs 0.000 claims description 4
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- FKASAVXZZLJTNX-UHFFFAOYSA-N 2-(dimethylamino)acetic acid;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(O)=O FKASAVXZZLJTNX-UHFFFAOYSA-N 0.000 claims description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 claims description 3
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- 108010077895 Sarcosine Proteins 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims 2
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 229940043230 sarcosine Drugs 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 18
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 abstract description 10
- 239000002904 solvent Substances 0.000 abstract description 8
- 239000003054 catalyst Substances 0.000 abstract description 5
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 239000002699 waste material Substances 0.000 abstract description 3
- 150000003839 salts Chemical class 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 239000007787 solid Substances 0.000 description 36
- 238000004440 column chromatography Methods 0.000 description 26
- 239000003208 petroleum Substances 0.000 description 26
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 25
- 239000012043 crude product Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 5
- 150000001879 copper Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- LWJIVGBLQDNDGH-UHFFFAOYSA-N N-(2-iodophenyl)-N-methylbut-2-ynamide Chemical compound IC1=C(C=CC=C1)N(C(C#CC)=O)C LWJIVGBLQDNDGH-UHFFFAOYSA-N 0.000 description 2
- QXHRCZIYCSNLPC-UHFFFAOYSA-N n-(2-iodophenyl)-n-methylhept-2-ynamide Chemical compound CCCCC#CC(=O)N(C)C1=CC=CC=C1I QXHRCZIYCSNLPC-UHFFFAOYSA-N 0.000 description 2
- 229960003540 oxyquinoline Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- TUGFSQNHIXVUBI-UHFFFAOYSA-N triazolo[4,5-f]quinoxalin-4-one Chemical class O=C1C=C2N=CC=NC2=C2C1=NN=N2 TUGFSQNHIXVUBI-UHFFFAOYSA-N 0.000 description 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 description 1
- 0 CN(c1ccccc1NC1=*c2ccccc2)C1=O Chemical compound CN(c1ccccc1NC1=*c2ccccc2)C1=O 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- VEHQVMFZFRMKJA-UHFFFAOYSA-N N-(2-bromophenyl)-N-methyl-3-phenylprop-2-ynamide Chemical compound CN(C(=O)C#Cc1ccccc1)c1ccccc1Br VEHQVMFZFRMKJA-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- QQIFJGTXMQWMNS-UHFFFAOYSA-N n-(2-iodophenyl)-3-phenylprop-2-ynamide Chemical compound IC1=CC=CC=C1NC(=O)C#CC1=CC=CC=C1 QQIFJGTXMQWMNS-UHFFFAOYSA-N 0.000 description 1
- QAZVYPJIOMPQHS-UHFFFAOYSA-N n-benzyl-n-(2-iodophenyl)-3-phenylprop-2-ynamide Chemical compound IC1=CC=CC=C1N(C(=O)C#CC=1C=CC=CC=1)CC1=CC=CC=C1 QAZVYPJIOMPQHS-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
技术领域 technical field
本发明属于化学合成领域，具体涉及三氮唑喹喔啉酮衍生物的合成方法。The invention belongs to the field of chemical synthesis, and in particular relates to a synthesis method of triazole quinoxalinone derivatives.
背景技术 Background technique
杂环化合物是有机化学重要的组成部分，是一类非常重要的有机化合物，其在生物化工、日化、医药、材料等诸多方面具有广泛的应用，如三氮唑喹喔啉酮衍生物III具有较好的镇静催眠作用，而IV则具有良好地烟酸样扩张血管的作用(参考文献：(1).J.Med.Chem.2009，52，2587.(2)Eur.J.Med.Chem.2002，37，565.(3)Eur.J.Med.Chem.1998，33，113)。传统的合成杂环化合物的方法一般是多步合成，效率低下，且很难引入不同的取代基团。近年来，发展新的、高效的合成杂环化合物的方法越来越成为有机化学家关注的焦点。串联反应在现代合成方法学上为杂环合成提供了一个有效的手段，能缩短反应路线提高原子经济性，避免使用有毒溶剂，减少废弃物，提高反应效率。本发明提供了一种利用串联反应高效合成三氮唑喹喔啉酮衍生物的方法。Heterocyclic compounds are an important part of organic chemistry and a very important class of organic compounds. They are widely used in many aspects such as biochemical industry, daily chemical industry, medicine, materials, etc., such as triazole quinoxalinone derivatives III It has a good sedative and hypnotic effect, while IV has a good niacin-like dilating effect on blood vessels (references: (1). J. Med. Chem. 2009, 52, 2587. (2) Eur. J. Med. Chem. 2002, 37, 565. (3) Eur. J. Med. Chem. 1998, 33, 113). The traditional methods for synthesizing heterocyclic compounds are generally multi-step synthesis, which is inefficient and difficult to introduce different substituent groups. In recent years, the development of new and efficient methods for the synthesis of heterocyclic compounds has increasingly become the focus of attention of organic chemists. The tandem reaction provides an effective method for heterocyclic synthesis in modern synthetic methodology, which can shorten the reaction route and improve atom economy, avoid the use of toxic solvents, reduce waste, and improve reaction efficiency. The invention provides a method for efficiently synthesizing triazole quinoxalinone derivatives by utilizing cascade reactions.
发明内容 Contents of the invention
本发明的目的是提供一种合成三氮唑喹喔啉酮衍生物的方法。The purpose of this invention is to provide a kind of method of synthesizing triazole quinoxalinone derivative.
具体的技术方案如下：The specific technical scheme is as follows:
一种具有式II结构的三氮唑喹喔啉酮衍生物的合成方法，在有机溶剂的环境中，铜盐或铜盐/配体组合作为催化剂，在碱存在或没有碱存在的情况下，将具有式I结构的化合物与NaN3串联反应，合成所述三氮唑喹喔啉酮衍生物，A method for synthesizing triazoloquinoxalinone derivatives with the structure of formula II, in the environment of organic solvents, copper salt or copper salt/ligand combination is used as a catalyst, in the presence or absence of a base, The compound with the structure of formula I is reacted in series with NaN to synthesize the triazoloquinoxalinone derivative,
其中：in:
R1＝H，CN，NO2，CF3，COOR’，羰基，C1～C12烷基，C1～C12芳烷基，芳基，OR’，杂环基团；R 1 =H, CN, NO 2 , CF 3 , COOR', carbonyl, C 1 -C 12 alkyl, C 1 -C 12 aralkyl, aryl, OR', heterocyclic group;
R2＝芳基，杂环基团，C1～C12烷基，C1～C12芳烷基，C1～C12烷氧基；R 2 = aryl, heterocyclic group, C 1 -C 12 alkyl, C 1 -C 12 aralkyl, C 1 -C 12 alkoxy;
R3＝H，C1～C12烷基，C1～C12芳烷基，烯丙基，芳基；R 3 ＝H, C 1 ~C 12 alkyl, C 1 ~C 12 aralkyl, allyl, aryl;
X4＝Cl，Br，I； X4 = Cl, Br, I;
R’＝C1～C12烷基。R'=C 1 -C 12 alkyl.
优选地，所述催化剂铜盐相对于式I结构的化合物的用量的摩尔百分比为2％到50％，NaN3与所述式I结构的化合物的摩尔比为1∶1到2.0∶1，所述配体与铜盐的摩尔比为1∶1到5∶1。Preferably, the molar percentage of the catalyst copper salt relative to the compound of the formula I is 2% to 50%, and the molar ratio of NaN to the compound of the formula I is 1:1 to 2.0:1, so The molar ratio of the ligand to the copper salt is 1:1 to 5:1.
优选地，其中Preferably, where
R1＝H，CN，NO2，CF3，COOR’，羰基，C1～C4烷基，芳基，OR’；R 1 =H, CN, NO 2 , CF 3 , COOR', carbonyl, C 1 ~C 4 alkyl, aryl, OR';
R2＝芳基，噻吩，C1～C4烷基，环己基，C1～C4芳烷基，C1～C4烷氧基；R 2 = aryl, thiophene, C 1 -C 4 alkyl, cyclohexyl, C 1 -C 4 aralkyl, C 1 -C 4 alkoxy;
R3＝H，C1～C4烷基，C1～C4芳烷基，烯丙基，芳基；R 3 =H, C 1 ~C 4 alkyl, C 1 ~C 4 aralkyl, allyl, aryl;
R’＝C1～C4烷基。R'=C 1 -C 4 alkyl.
优选地，所述串联反应的进行温度在40～150℃之间，反应时间1小时-48小时，产物的收率为20-100％不等。Preferably, the temperature for the series reaction is between 40°C and 150°C, the reaction time is 1 hour to 48 hours, and the yield of the product ranges from 20% to 100%.
优选地，所述的碱为K2CO3，Cs2CO3，K3PO4，NaOH或KOH，所述的有机溶剂为二甲基亚砜，N，N-二甲基甲酰胺，N，N-二甲基乙酰胺，1，4-二氧六环或乙腈。Preferably, the base is K 2 CO 3 , Cs 2 CO 3 , K 3 PO 4 , NaOH or KOH, and the organic solvent is dimethyl sulfoxide, N,N-dimethylformamide, N , N-dimethylacetamide, 1,4-dioxane or acetonitrile.
优选地，所述的配体为L-脯氨酸，L-4-羟基脯氨酸，N-甲基甘氨酸，N，N-二甲基甘氨酸盐酸盐，8-羟基喹啉，2-吡啶甲酸，2-吡咯甲酸，N，N’-二甲基乙二胺或啡啰啉，所述催化剂铜盐为CuI，CuBr，CuCl，Cu2O或CuSO4。Preferably, the ligand is L-proline, L-4-hydroxyproline, N-methylglycine, N,N-dimethylglycine hydrochloride, 8-hydroxyquinoline, 2- picolinic acid, 2-pyrrole carboxylic acid, N,N'-dimethylethylenediamine or phenanthroline, and the catalyst copper salt is CuI, CuBr, CuCl, Cu 2 O or CuSO 4 .
优选地，所述催化剂铜盐为CuI。Preferably, the catalyst copper salt is CuI.
上述反应的反应通式如下：The general reaction formula of above-mentioned reaction is as follows:
本发明的优点是：本发明提供了一种利用串联反应高效合成三氮唑喹喔啉酮衍生物的方法，串联反应在现代合成方法学上为杂环合成提供了一个有效的手段，能缩短反应路线提高原子经济性，避免使用有毒溶剂，减少废弃物，提高反应效率。The advantage of the present invention is: the present invention provides a kind of method utilizing tandem reaction to efficiently synthesize triazole quinoxalinone derivatives, and tandem reaction provides an effective means for heterocyclic synthesis in modern synthesis methodology, can shorten The reaction route improves atom economy, avoids the use of toxic solvents, reduces waste, and improves reaction efficiency.
具体实施方式 Detailed ways
通过下述具体实施例将有助于理解本发明，但并不限制本发明的内容。The following specific examples will help to understand the present invention, but do not limit the content of the present invention.
实施例1Example 1
底物I(X＝I)与NaN3的反应(方法A)Reaction of substrate I (X=I) with NaN 3 (Method A)
在一个一端密封的反应管内，加入N-(2-碘苯基)-N-甲基-2-丁炔酰胺(1.0mmol)，然后加入NaN3(1.1mmol)，K2CO3(2.0mmol)，CuI(0.05mmol)，1.0ml DMSO作为溶剂，在氩气或氮气保护下，于80℃下搅拌反应6h，用10毫升水稀释反应混合液，有大量固体析出，过滤，滤液用10毫升乙酸乙酯萃取两次，合并有机相，干燥后减压旋干得淡黄色固体，将所得固体和滤饼合并柱层析(淋洗液石油醚∶乙酸乙酯＝10∶1)得产物200mg，产率94％；1H NMR(CDCl3，400MHz)δ8.50(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.58(td，J＝8.0Hz，J＝1.2Hz，1H)，7.39-7.42(m，2H)，3.70(s，3H)，2.80(s，3H )；13C NMR(CDCl3，125MHz)δ154.8，130.3，129.2，124.1，122.4，116.7，115.6，28.6，11.4；ESI-MS m/z 215.1[M+H]+.In a reaction tube sealed at one end, N-(2-iodophenyl)-N-methyl-2-butynamide (1.0mmol) was added, followed by NaN 3 (1.1mmol), K 2 CO 3 (2.0mmol ), CuI (0.05mmol), 1.0ml DMSO as a solvent, under the protection of argon or nitrogen, stir the reaction at 80°C for 6h, dilute the reaction mixture with 10ml of water, a large amount of solid precipitates, filter, and use 10ml of the filtrate Ethyl acetate was extracted twice, the organic phases were combined, dried and spin-dried under reduced pressure to obtain a light yellow solid, and the resulting solid and filter cake were combined for column chromatography (petroleum ether:ethyl acetate=10:1) to obtain 200 mg of the product , yield 94%; 1 H NMR (CDCl 3 , 400MHz) δ8.50 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.58 (td, J=8.0Hz, J=1.2Hz, 1H) , 7.39-7.42 (m, 2H), 3.70 (s, 3H), 2.80 (s, 3H ); 13 C NMR (CDCl 3 , 125 MHz) δ154.8, 130.3, 129.2, 124.1, 122.4, 116.7, 115.6, 28.6 , 11.4; ESI-MS m/z 215.1[M+H] + .
实施例2Example 2
按照如方法A所述，N-(2-碘苯基)-N-甲基-2-庚炔酰胺(1.0mmol)与NaN3(1.5mmol)、Cs2CO3(2.0mmol)在DMA(1mL)中，90℃下搅拌6h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯，得白色固体235mg，产率：92％；1H NMR(CDCl3，400MHz)δ8.50(d，J＝7.6Hz，1H)，7.56(td，J＝8.0Hz，J＝1.2Hz，1H)，7.38-7.42(m，2H)，3.70(s，3H)，3.19(t，J＝8.0Hz，2H)，1.78-1.86(m，2H)，1.40-1.50(m，2H)，0.98(t，J＝4.8Hz，3H)；13C NMR(CDCl3，125MHz)δ154.7，150.6，130.3，129.1，124.0，122.3，122.2，116.7，115.5，31.4，28.6，25.4，22.4，13.8；ESI-MSm/z 257.1[M+H]+.N-(2-iodophenyl)-N-methyl-2-heptyne amide (1.0 mmol) was mixed with NaN 3 (1.5 mmol), Cs 2 CO 3 (2.0 mmol) in DMA ( 1 mL), stirred at 90°C for 6h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 235 mg of white solid, yield: 92%; 1 H NMR (CDCl 3 , 400 MHz) δ8.50 (d, J=7.6 Hz, 1H), 7.56(td, J=8.0Hz, J=1.2Hz, 1H), 7.38-7.42(m, 2H), 3.70(s, 3H), 3.19(t, J=8.0Hz, 2H), 1.78- 1.86 (m, 2H), 1.40-1.50 (m, 2H), 0.98 (t, J=4.8Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.7, 150.6, 130.3, 129.1, 124.0, 122.3 , 122.2, 116.7, 115.5, 31.4, 28.6, 25.4, 22.4, 13.8; ESI-MSm/z 257.1[M+H] + .
实施例3Example 3
按照如方法A所述，4-环己基-N-(2-碘苯基)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(2.0mmol)、K3PO4(2.0mmol)在DMF中，90℃下搅拌6h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得黄色固体255mg，产率：67％；1H NMR(CDCl3，400MHz)δ8.51(dd，J＝8.8Hz，J＝2.0Hz，1H)，7.56(td，J＝8.0Hz，J＝1.6Hz，1H)，7.38-7.42(m，2H)，3.70(s，3H)，3.09(d，J＝7.2Hz，2H)，1.83-1.93(m，1H)，1.61-1.75(m，5H)，1.15-1.28(m，5H)；13C NMR(CDCl3，125MHz)δ154.7，149.4，130.2，129.1，124.0，122.7，122.3，116.7，115.5，38.3，33.0，32.9，28.6，26.4，26.1；ESI-MS m/z 297.2[M+H]+.4-Cyclohexyl-N-(2-iodophenyl)-N-methyl-2-butynamide (1.0 mmol) was mixed with NaN 3 (2.0 mmol), K 3 PO 4 (2.0 mmol) in DMF, stirred at 90°C for 6h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 255 mg of yellow solid, yield: 67%; 1 H NMR (CDCl 3 , 400 MHz) δ8.51 (dd, J=8.8Hz, J =2.0Hz, 1H), 7.56(td, J=8.0Hz, J=1.6Hz, 1H), 7.38-7.42(m, 2H), 3.70(s, 3H), 3.09(d, J=7.2Hz, 2H ), 1.83-1.93 (m, 1H), 1.61-1.75 (m, 5H), 1.15-1.28 (m, 5H); 13 C NMR (CDCl 3 , 125MHz) δ154.7, 149.4, 130.2, 129.1, 124.0, 122.7, 122.3, 116.7, 115.5, 38.3, 33.0, 32.9, 28.6, 26.4, 26.1; ESI-MS m/z 297.2[M+H] + .
实施例4Example 4
按照如方法A所述，N-(2-碘苯基)-N-甲基-2-己炔酰胺(1.0mmol)与NaN3(1.2mmol)、Cu2O(0.02mmol)，NaOH(2.0mmol)在DMSO中，90℃下搅拌16h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得黄色固体213mg，产率：88％；1H NMR(CDCl3，400MHz)δ8.51(d，J＝8.0Hz，1H)，7.56(td，J＝8.0Hz，J＝1.2Hz，1H)，7.39-7.42(m，2H)，3.70(s，3H)，3.17(t，J＝8.0Hz，2H)，1.83-1.90(m，2H)，1.03(t，J＝7.2Hz，3H)；13C NMR(CDCl3，125MHz)δ154.7，130.3，129.1，124.0，122.4，116.7，115.5，28.6，27.6，22.7，13.8；ESI-MS m/z 243.3[M+H]+.As described in method A, N-(2-iodophenyl)-N-methyl-2-hexyne amide (1.0 mmol) was mixed with NaN 3 (1.2 mmol), Cu 2 O (0.02 mmol), NaOH (2.0 mmol) in DMSO was stirred at 90 °C for 16 h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 213 mg of yellow solid, yield: 88%; 1 H NMR (CDCl 3 , 400 MHz) δ8.51 (d, J=8.0 Hz, 1H ), 7.56(td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42(m, 2H), 3.70(s, 3H), 3.17(t, J=8.0Hz, 2H), 1.83-1.90 (m, 2H), 1.03 (t, J=7.2Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.7, 130.3, 129.1, 124.0, 122.4, 116.7, 115.5, 28.6, 27.6, 22.7, 13.8 ;ESI-MS m/z 243.3[M+H] + .
实施例5Example 5
按照如方法A所述，4-(苄氧基)-N-(2-碘-5-苯基-苯基)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(1.2mmol)，CuSO4(0.5mmol)，在DMSO中，90℃下搅拌16h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体334mg，产率：73％；1H NMR(CDCl3，400MHz)δ8.55(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.59(td，J＝8.0Hz，J＝1.2Hz，1H)，7.41-7.45(m，4H)，7.33(t，J＝7.6Hz，2H)，7.24-7.28(m，6H)，5.11(s，3H)，4.74(s，2H)，3.72(s，3H)；13C NMR(CDCl3，125MHz)δ154.0，145.8，138.0，130.2，129.5，128.5，128.4，128.3，128.2，128.1，128.0，127.6，124.3，123.6，122.0，116.8，115.6，62.2，28.8；ESI-MS m/z 397.2[M+H]+.As described in method A, 4-(benzyloxy)-N-(2-iodo-5-phenyl-phenyl)-N-methyl-2-butynamide (1.0 mmol) was mixed with NaN 3 (1.2 mmol), CuSO 4 (0.5 mmol), in DMSO, stirred at 90° C. for 16 h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 334 mg of white solid, yield: 73%; 1 H NMR (CDCl 3 , 400MHz) δ8.55 (dd, J=8.8Hz, J =1.6Hz, 1H), 7.59(td, J=8.0Hz, J=1.2Hz, 1H), 7.41-7.45(m, 4H), 7.33(t, J=7.6Hz, 2H), 7.24-7.28(m , 6H), 5.11(s, 3H), 4.74(s, 2H), 3.72(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.0, 145.8, 138.0, 130.2, 129.5, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.6, 124.3, 123.6, 122.0, 116.8, 115.6, 62.2, 28.8; ESI-MS m/z 397.2[M+H] + .
实施例6Example 6
按照如方法A所述，N-(2-碘-5-丙酰基苯基)-N-甲基-3-苯丙炔酰胺(1.0mmol)与NaN3(1.5mmol)、K2CO3(2.0mmol)，CuI(0.5mmol)在二氧六环(1mL)中，100℃下搅拌48h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体66mg，产率：20％；1H NMR(CDCl3，400MHz)δ8.60(dd，J＝8.4Hz，J＝1.6Hz，1H)，8.36(d，J＝7.2Hz，2H)，7.61(td，J＝8.0Hz，J＝1.6Hz，1H)，7.50-7.54(m，2H)，7.43-7.47(m，3H)，3.75(s，3H)，2.10(q，J＝7.2Hz，2H)，1.03(t，J＝7.2Hz，3H)；13C NMR(CDCl3，125MHz)δ154.3，148.6，130.2，129.4，129.3，128.3，124.2，122.2，121.6，116.9，115.5，29.1，20.0，14.2；ESI-MS m/z 333.1[M+H]+.N-(2-iodo-5-propionylphenyl)-N-methyl-3-phenylpropynamide (1.0 mmol) was mixed with NaN 3 (1.5 mmol), K 2 CO 3 ( 2.0 mmol), CuI (0.5 mmol) in dioxane (1 mL), stirred at 100° C. for 48 h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 66 mg of white solid, yield: 20%; 1 H NMR (CDCl 3 , 400MHz) δ8.60 (dd, J=8.4Hz, J =1.6Hz, 1H), 8.36(d, J=7.2Hz, 2H), 7.61(td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54(m, 2H), 7.43-7.47(m , 3H), 3.75(s, 3H), 2.10(q, J=7.2Hz, 2H), 1.03(t, J=7.2Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.3, 148.6, 130.2, 129.4, 129.3, 128.3, 124.2, 122.2, 121.6, 116.9, 115.5, 29.1, 20.0, 14.2; ESI-MS m/z 333.1[M+H] + .
实施例7Example 7
按照如方法A所述，N-(2-碘苯基)-N-甲基-5-苯基-2-戊炔酰胺(1.0mmol)与NaN3(1.5mmol)、Cs2CO3(2.0mmol)，CuI(0.1mmol)，配体N，N’-二甲基乙二胺或啡啰啉(0.2mmol)在90℃下搅拌26h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体279mg，产率：90％；1H NMR(CDCl3，400MHz)δ8.58(dd，J＝8.8Hz，J＝1.6Hz，1H)，8.25(d，J＝8.0Hz，2H)，7.59(td，J＝8.0Hz，J＝1.2Hz，1H)，7.41-7.44(m，2H)，7.32(d，J＝8.0Hz，2H)，7.25(m，5H)，3.74(s，3H)，2.43(t，J＝6.8Hz，2H)，2.12(t，J＝6.8Hz，2H)；13C NMR(CDCl3，125MHz)δ154.3，148.8，139.4，130.2，129.4，129.2，129.1，128.5，128.3，127.4，127.0，126.4，124.1，122.2，116.9，115.5，29.1，21.4，20.5；ESI-MS m/z 305.1[M+H]+.N-(2-iodophenyl)-N-methyl-5-phenyl-2-pentyne amide (1.0 mmol) was mixed with NaN 3 (1.5 mmol), Cs 2 CO 3 (2.0 mmol), CuI (0.1mmol), ligand N, N'-dimethylethylenediamine or phenanthroline (0.2mmol) were stirred at 90°C for 26h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 279 mg of white solid, yield: 90%; 1 H NMR (CDCl 3 , 400 MHz) δ8.58 (dd, J=8.8Hz, J =1.6Hz, 1H), 8.25(d, J=8.0Hz, 2H), 7.59(td, J=8.0Hz, J=1.2Hz, 1H), 7.41-7.44(m, 2H), 7.32(d, J =8.0Hz, 2H), 7.25(m, 5H), 3.74(s, 3H), 2.43(t, J=6.8Hz, 2H), 2.12(t, J=6.8Hz, 2H); 13 C NMR (CDCl 3 , 125MHz) δ154.3, 148.8, 139.4, 130.2, 129.4, 129.2, 129.1, 128.5, 128.3, 127.4, 127.0, 126.4, 124.1, 122.2, 116.9, 115.5, 29.1, 21.4, 20.5; zESI-MS m/ 305.1[M+H] + .
实施例8Example 8
按照如方法A所述，N-(2-碘苯基)-3-(2-噻吩基)-N-甲基丙炔酰胺(1.0mmol)与NaN3(1.5mmol)、CuCl(0.2mmol)在DMSO中，100℃下搅拌16h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体266mg，产率：93％；1H NMR(CDCl3，400MHz)δ8.58(dd，J＝8.4Hz，J＝1.6Hz，1H)，8.35(d，J＝8.8Hz，2H)，7.59(td，J＝8.4Hz，J＝1.6Hz，1H)，7.26(m，1H)，7.04(d，J＝9.2Hz，1H)，6.99(d，J＝8.8Hz，1H)，3.74(s，3H)；13C NMR(CDCl3，125MHz)δ160.5，154.4，148.5，130.7，130.1，129.3，124.1，122.3，121.0，116.8，，113.8，29.1；ESI-MS m/z 283.0[M+H]+.According to method A, N-(2-iodophenyl)-3-(2-thienyl)-N-methylpropynamide (1.0mmol) was mixed with NaN 3 (1.5mmol), CuCl (0.2mmol) In DMSO, stirred at 100 °C for 16 h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 266 mg of white solid, yield: 93%; 1 H NMR (CDCl 3 , 400MHz) δ8.58 (dd, J=8.4Hz, J =1.6Hz, 1H), 8.35(d, J=8.8Hz, 2H), 7.59(td, J=8.4Hz, J=1.6Hz, 1H), 7.26(m, 1H), 7.04(d, J=9.2 Hz, 1H), 6.99(d, J=8.8Hz, 1H), 3.74(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ160.5, 154.4, 148.5, 130.7, 130.1, 129.3, 124.1, 122.3 , 121.0, 116.8, , 113.8, 29.1; ESI-MS m/z 283.0[M+H] + .
实施例9Example 9
按照如方法A所述，N-(2-碘-4-甲基苯)-N-甲基-3-苯丙炔酰胺(1.0mmol)与NaN3(1.2mmol)、CuI(0.05mmol)在DMSO中，90℃下搅拌15h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体223mg，产率：77％；1H NMR(CDCl3，400MHz)δ8.40(s，1H)，8.36(d，J＝7.2Hz，2H)，7.50-7.54(m，2H)，7.43-7.47(m，1H)，7.39(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.31(d，J＝8.8Hz，1H)，3.72(s，3H)，2.53(s，3H)；13C NMR(CDCl3，125MHz)δ154.1，148.5，134.6，130.3，129.4，129.3，129.2，128.3，127.9，121.9，121.7，116.9，115.3，29.1，20.9；ESI-MS m/z 291.0[M+H]+.As described in Method A, N-(2-iodo-4-methylbenzene)-N-methyl-3-phenylpropynamide (1.0mmol) was mixed with NaN 3 (1.2mmol), CuI (0.05mmol) in In DMSO, stir at 90°C for 15h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 223 mg of white solid, yield: 77%; 1 H NMR (CDCl 3 , 400 MHz) δ8.40 (s, 1H), 8.36 (d , J=7.2Hz, 2H), 7.50-7.54(m, 2H), 7.43-7.47(m, 1H), 7.39(dd, J=8.8Hz, J=1.6Hz, 1H), 7.31(d, J= 8.8Hz, 1H), 3.72(s, 3H), 2.53(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.1, 148.5, 134.6, 130.3, 129.4, 129.3, 129.2, 128.3, 127.9, 121.9 , 121.7, 116.9, 115.3, 29.1, 20.9; ESI-MS m/z 291.0[M+H] + .
实施例10Example 10
按照如方法A所述，N-(2-碘-4-丙氧基苯)-N-甲基-3-苯丙炔酰胺(1.0mmol)与NaN3(2.0mmol)、CuI(0.02mmol)在DMSO中，90℃下搅拌35h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体238mg，产率：73％；1H NMR(CDCl3，400MHz)δ8.36(d，J＝7.2Hz，2H)，8.07(d，J＝2.8Hz，1H)，7.52(t，J＝7.2Hz，2H)，7.45(t，J＝7.2Hz，1H)，7.36(d，J＝9.2Hz，1H)，7.16(dd，J＝9.2Hz，J＝2.8Hz，1H)，3.97(t，J＝7.2Hz，2H)，3.73(s，3H)，1.32(m，2H)，0.89(t，J＝6.8Hz，3H)；13C NMR(CDCl3，125MHz)δ156.4，153.8，148.6，129.4，129.3，128.3，123.9，122.7，121.9，117.4，116.8，100.3，56.1，29.2，17.3，14.1；ESI-MS m/z 335.1[M+H]+.As described in method A, N-(2-iodo-4-propoxybenzene)-N-methyl-3-phenylpropynamide (1.0mmol) was mixed with NaN 3 (2.0mmol), CuI (0.02mmol) In DMSO, stirred at 90 °C for 35 h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 238 mg of white solid, yield: 73%; 1 H NMR (CDCl 3 , 400 MHz) δ8.36 (d, J=7.2 Hz, 2H ), 8.07(d, J=2.8Hz, 1H), 7.52(t, J=7.2Hz, 2H), 7.45(t, J=7.2Hz, 1H), 7.36(d, J=9.2Hz, 1H), 7.16(dd, J=9.2Hz, J=2.8Hz, 1H), 3.97(t, J=7.2Hz, 2H), 3.73(s, 3H), 1.32(m, 2H), 0.89(t, J=6.8 Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ156.4, 153.8, 148.6, 129.4, 129.3, 128.3, 123.9, 122.7, 121.9, 117.4, 116.8, 100.3, 56.1, 29.2, 17.3, 14.1; ESI- MS m/z 335.1[M+H] + .
实施例11Example 11
按照方法A所述，N-(2-碘-4-甲基苯)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(2.0mmol)、CuI(0.2mmol)在90℃下搅拌25h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得淡黄色固体151mg，产率：66％；1HNMR(CDCl3，400MHz)δ8.31(s，1H)，7.35(dd，J＝8.4Hz，J＝1.2Hz，1H)，7.28(d，J＝8.4Hz，1H)，3.67(s，3H)，2.79(s，3H)，2.50(S，3H)；13C NMR(CDCl3，125MHz)δ154.7，146.0，134.4，130.1，128.1，122.7，122.0，116.7，115.4，28.6，20.8，11.4；ESI-MS m/z 229.1[M+H]+.According to method A, N-(2-iodo-4-methylbenzene)-N-methyl-2-butynamide (1.0mmol) was mixed with NaN 3 (2.0mmol), CuI (0.2mmol) at 90°C Under stirring for 25h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 151 mg of light yellow solid, yield: 66%; 1 HNMR (CDCl 3 , 400 MHz) δ8.31 (s, 1H), 7.35 (dd , J=8.4Hz, J=1.2Hz, 1H), 7.28(d, J=8.4Hz, 1H), 3.67(s, 3H), 2.79(s, 3H), 2.50(S, 3H); 13 C NMR (CDCl 3 , 125MHz)δ154.7, 146.0, 134.4, 130.1, 128.1, 122.7, 122.0, 116.7, 115.4, 28.6, 20.8, 11.4; ESI-MS m/z 229.1[M+H] + .
实施例12Example 12
按照方法A所述，N-(2-碘-4-(三氟甲基)苯)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(2.0mmol)、CuI(0.1mmol)在DMSO中，60℃下搅拌36h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得白色固体223mg，产率：79％；1H NMR(CDCl3，400MHz)δ8.78(d，J＝1.2Hz，1H)，7.80(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.51(d，J＝8.8Hz，1H)，3.73(s，3H)，2.80(s，3H)；13C NMR(CDCl3，125MHz)δ154.6，146.7，132.7，126.6，126.3，125.9，125.8，124.4，122.6，122.2，122.1，116.1，114.4，114.3，28.9，11.4；ESI-MS m/z 283.1[M+H]+.N-(2-iodo-4-(trifluoromethyl)benzene)-N-methyl-2-butynamide (1.0 mmol) was mixed with NaN 3 (2.0 mmol), CuI (0.1 mmol) as described in method A ) in DMSO, stirred at 60°C for 36h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 223 mg of white solid, yield: 79%; 1 H NMR (CDCl 3 , 400 MHz) δ8.78 (d, J=1.2 Hz, 1H ), 7.80(dd, J=8.8Hz, J=1.6Hz, 1H), 7.51(d, J=8.8Hz, 1H), 3.73(s, 3H), 2.80(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.6, 146.7, 132.7, 126.6, 126.3, 125.9, 125.8, 124.4, 122.6, 122.2, 122.1, 116.1, 114.4, 114.3, 28.9, 11.4; ESI-MS m/z 283.1 [M+H] + .
实施例13Example 13
按照方法A所述，N-(2-碘-4-硝基苯)-N-甲基-2-丁炔酰胺(344mg，1.0mmol)与NaN3(98mg，1.5mmol)、CuI(0.1mmol)在DMSO中，40℃下搅拌33h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得黄色固体110mg，产率：42％；1H NMR(CDCl3，400MHz)δ9.37(d，J＝2.4Hz，1H)，8.43(dd，J＝9.2Hz，J＝2.4Hz，1H)，7.53(d，J＝9.2Hz，1H)，3.76(s，3H)，2.81(s，3H)；13C NMR(CDCl3，125MHz)δ154.4，147.2，143.3，134.8，124.1，122.4，122.0，116.1，112.8，58.5，53.4，29.2，18.4，11.3；ESI-MS m/z 260.1[M+H]+.N-(2-iodo-4-nitrophenyl)-N-methyl-2-butynamide (344 mg, 1.0 mmol) was mixed with NaN 3 (98 mg, 1.5 mmol), CuI (0.1 mmol) as described in method A ) in DMSO, stirred at 40°C for 33h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 110 mg of yellow solid, yield: 42%; 1 H NMR (CDCl 3 , 400 MHz) δ9.37 (d, J=2.4 Hz, 1H ), 8.43(dd, J=9.2Hz, J=2.4Hz, 1H), 7.53(d, J=9.2Hz, 1H), 3.76(s, 3H), 2.81(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.4, 147.2, 143.3, 134.8, 124.1, 122.4, 122.0, 116.1, 112.8, 58.5, 53.4, 29.2, 18.4, 11.3; ESI-MS m/z 260.1[M+H] + .
实施例14Example 14
按照方法A所述，N-(4-氰基-2-碘苯)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(1.5mmol)、K2CO3(2.0mmol)，CuI(0.1mmol)在DMSO中，90℃下搅拌3h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得白色固体189mg，产率：79％；1H NMR(CDCl3，400MHz)δ8.79(d，J＝1.6Hz，1H)，7.82(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.49(d，J＝8.8Hz，1H)，3.72(s，3H)，2.80(s，3H)；13C NMR(CDCl3，125MHz)δ154.4，147.0，133.5，132.4，122.4，120.5，117.2，116.5，107.7，58.5，28.9，18.4，11.3；ESI-MS m/z 240.1[M+H]+.N-(4-cyano-2-iodobenzene)-N-methyl-2-butynamide (1.0 mmol) was mixed with NaN 3 (1.5 mmol), K 2 CO 3 (2.0 mmol) as described in method A , CuI (0.1 mmol) in DMSO was stirred at 90° C. for 3 h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 189 mg of white solid, yield: 79%; 1 H NMR (CDCl 3 , 400 MHz) δ8.79 (d, J=1.6 Hz, 1H ), 7.82(dd, J=8.8Hz, J=1.6Hz, 1H), 7.49(d, J=8.8Hz, 1H), 3.72(s, 3H), 2.80(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.4, 147.0, 133.5, 132.4, 122.4, 120.5, 117.2, 116.5, 107.7, 58.5, 28.9, 18.4, 11.3; ESI-MS m/z 240.1[M+H] + .
实施例15Example 15
按照方法A所述，N-(2-碘苯基)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(1.5mmol)、K2CO3(2.0mmol)，CuI(0.2mmol)在DMSO中，120℃下搅拌46h。粗产物经柱层析(10∶1石油醚∶乙酸乙酯)提纯得白色固体42mg，产率：22％；1H NMR(CDCl3，400MHz)δ8.80(br，1H)，8.50(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.58(td，J＝8.0Hz，J＝1.2Hz，1H)，7.39-7.42(m，2H)，2.80(s，3H)；13C NMR(CDCl3，125MHz)δ154.8，130.3，129.2，124.1，122.4，116.7，115.6，11.4；ESI-MS m/z 201.1[M+H]+.N-(2-iodophenyl)-N-methyl-2-butynamide (1.0 mmol) was mixed with NaN 3 (1.5 mmol), K 2 CO 3 (2.0 mmol), CuI (0.2 mmol) in DMSO was stirred at 120° C. for 46 h. The crude product was purified by column chromatography (10:1 petroleum ether: ethyl acetate) to obtain 42 mg of white solid, yield: 22%; 1 H NMR (CDCl 3 , 400 MHz) δ8.80 (br, 1H), 8.50 (dd , J=8.8Hz, J=1.6Hz, 1H), 7.58(td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42(m, 2H), 2.80(s, 3H); 13 C NMR (CDCl 3 , 125MHz)δ154.8, 130.3, 129.2, 124.1, 122.4, 116.7, 115.6, 11.4; ESI-MS m/z 201.1[M+H] + .
实施例16Example 16
按照如方法A所述，N-(2-碘苯基)-3-苯丙炔酰胺(1.0mmol)与NaN3(1.5mmol)、CuI(0.2mmol)在DMSO中，120℃下搅拌46h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体56mg，产率：20％；1H NMR(CDCl3，400MHz)δ8.80(br，1H)，8.60(dd，J＝8.4Hz，J＝1.6Hz，1H)，8.36(d，J＝7.2Hz，2H)，7.61(td，J＝8.0Hz，J＝1.6Hz，1H)，7.50-7.54(m，2H)，7.43-7.47(m，3H)；13C NMR(CDCl3，125MHz)δ154.3，148.6，130.2，129.4，129.3，128.3，124.2，122.2，121.6，116.9，115.5；ESI-MS m/z 263.1[M+H]+.As described in Method A, N-(2-iodophenyl)-3-phenylpropynamide (1.0 mmol) was stirred with NaN 3 (1.5 mmol), CuI (0.2 mmol) in DMSO at 120° C. for 46 h. The crude product was purified by column chromatography (3:1 dichloromethane: petroleum ether) to obtain 56 mg of white solid, yield: 20%; 1 H NMR (CDCl 3 , 400 MHz) δ8.80 (br, 1H), 8.60 (dd , J=8.4Hz, J=1.6Hz, 1H), 8.36(d, J=7.2Hz, 2H), 7.61(td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54(m, 2H ), 7.43-7.47 (m, 3H); 13 C NMR (CDCl 3 , 125 MHz) δ154.3, 148.6, 130.2, 129.4, 129.3, 128.3, 124.2, 122.2, 121.6, 116.9, 115.5; ESI-MS m/z 263.1[M+H] + .
实施例17Example 17
按照如方法A所述，N-(2-碘苯基)-3-苯基-N-丙基丙炔酰胺(1.0mmol)与NaN3(1.2mmol)、CuI(0.1mmol)在DMSO中，90℃下搅拌8h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体264mg，产率：87％；1H NMR(CDCl3，400MHz)δ8.61(dd，J＝8.4Hz，J＝1.2Hz，1H)，8.37(d，J＝7.2Hz，2H)，7.58(td，J＝8.4Hz，J＝1.6Hz，1H)，7.50-7.54(m，2H)，7.40-7.47(m，3H)，4.26(t，J＝8.0Hz，2H)，1.79-1.88(m，2H)，1.09(t，J＝7.6Hz，3H)；13C NMR(CDCl3，125MHz)δ154.1，148.5，129.4，129.3，128.3，124.0，122.3，121.6，117.1，115.5，43.8，20.7，11.3；ESI-MS m/z 305.2[M+H]+.N-(2-iodophenyl)-3-phenyl-N-propylpropynamide (1.0 mmol) with NaN3 (1.2 mmol), CuI (0.1 mmol) in DMSO as described in method A, Stir at 90°C for 8h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 264 mg of white solid, yield: 87%; 1 H NMR (CDCl 3 , 400MHz) δ8.61 (dd, J=8.4Hz, J =1.2Hz, 1H), 8.37(d, J=7.2Hz, 2H), 7.58(td, J=8.4Hz, J=1.6Hz, 1H), 7.50-7.54(m, 2H), 7.40-7.47(m , 3H), 4.26(t, J=8.0Hz, 2H), 1.79-1.88(m, 2H), 1.09(t, J=7.6Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.1, 148.5, 129.4, 129.3, 128.3, 124.0, 122.3, 121.6, 117.1, 115.5, 43.8, 20.7, 11.3; ESI-MS m/z 305.2[M+H] + .
实施例18Example 18
按照如方法A所述，N-苄基-N-(2-碘苯基)-3-苯丙炔酰胺(1.0mmol)与NaN3(1.2mmol)、CuI(0.1mmol)在DMSO中，90℃下搅拌8h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体327mg，产率：93％；1H NMR(CDCl3，400MHz)δ8.61(d，J＝8.0Hz，1H)，8.41(d，J＝7.2Hz，2H)，7.53(t，J＝7.2Hz，2H)，7.46(t，J＝7.2Hz，2H)，7.40(d，J＝7.6Hz，1H)，7.28-7.37(m，6H)，5.57(s，2H)；13C NMR(CDCl3，125MHz)δ154.6，149.0，135.2，129.5，129.4，129.2，129.0，128.4，127.8，126.6，124.3，122.3，121.5，117.0，116.4，58.5，45.8，18.4；ESI-MS m/z353.1[M+H]+.As described in method A, N-benzyl-N-(2-iodophenyl)-3-phenylpropynamide (1.0 mmol) with NaN 3 (1.2 mmol), CuI (0.1 mmol) in DMSO, 90 Stir at ℃ for 8h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 327 mg of white solid, yield: 93%; 1 H NMR (CDCl 3 , 400 MHz) δ8.61 (d, J=8.0 Hz, 1H ), 8.41(d, J=7.2Hz, 2H), 7.53(t, J=7.2Hz, 2H), 7.46(t, J=7.2Hz, 2H), 7.40(d, J=7.6Hz, 1H), 7.28-7.37 (m, 6H), 5.57 (s, 2H); 13 C NMR (CDCl 3 , 125 MHz) δ154.6, 149.0, 135.2, 129.5, 129.4, 129.2, 129.0, 128.4, 127.8, 126.6, 124.3, 122.3 , 121.5, 117.0, 116.4, 58.5, 45.8, 18.4; ESI-MS m/z353.1[M+H] + .
实施例19Example 19
按照如方法A所述，N-烯丙基-N-(2-碘苯基)-3-苯丙炔酰胺(1.0mmol)与NaN3(1.2mmol)、K2CO3(2.0mmol)，CuI(0.1mmol)在MeCN中，90℃下搅拌38h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体284mg，产率：94％；1H NMR(CDCl3，400MHz)δ8.61(dd，J＝8.0Hz，J＝1.2Hz，1H)，8.38(d，J＝1.6Hz，2H)，7.55(td，J＝8.4Hz，J＝1.6Hz，1H)，7.50-7.52(m，2H)，7.40-7.47(m，3H)，5.93-6.03(m，1H)，5.31(d，J＝10.0Hz，1H)，5.25(d，J＝17.2Hz，1H)，4.96-4.97(m，2H)；13C NMR(CDCl3，125MHz)δ154.0，148.8，130.8，129.4，129.3，129.2，128.3，124.2，122.3，121.5，118.1，117.0，116.1，44.4；ESI-MS m/z 303.2[M+H]+.N-allyl-N-(2-iodophenyl)-3-phenylpropynamide (1.0 mmol) with NaN 3 (1.2 mmol), K 2 CO 3 (2.0 mmol) as described in method A, CuI (0.1 mmol) was stirred in MeCN at 90 °C for 38 h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 284 mg of white solid, yield: 94%; 1 H NMR (CDCl 3 , 400MHz) δ8.61 (dd, J=8.0Hz, J =1.2Hz, 1H), 8.38(d, J=1.6Hz, 2H), 7.55(td, J=8.4Hz, J=1.6Hz, 1H), 7.50-7.52(m, 2H), 7.40-7.47(m , 3H), 5.93-6.03 (m, 1H), 5.31 (d, J=10.0Hz, 1H), 5.25 (d, J=17.2Hz, 1H), 4.96-4.97 (m, 2H); 13 C NMR ( CDCl 3 , 125MHz) δ154.0, 148.8, 130.8, 129.4, 129.3, 129.2, 128.3, 124.2, 122.3, 121.5, 118.1, 117.0, 116.1, 44.4; ESI-MS m/z 303.2[M+H] + .
实施例20Example 20
按照如方法A所述，4-(苄氧基)-N-(2-碘苯基)-N-甲基-2-丁炔酰胺(1.0mmol)与NaN3(1.2mmol)、K2CO3(2.0mmol)，CuI(0.05mmol)，配体2-吡啶甲酸或2-吡咯甲酸(0.1mmol)在DMSO(1mL)中，90℃下搅拌6h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体234mg，产率：73％；1H NMR(CDCl3，400MHz)δ8.55(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.59(td，J＝8.0Hz，J＝1.2Hz，1H)，7.41-7.45(m，4H)，7.33(t，J＝7.6Hz，2H)，7.24-7.28(m，1H)，5.11(s，3H)，4.74(s，2H)，3.72(s，3H)；13C NMR(CDCl3，125MHz)δ154.0，145.8，138.0，130.2，129.5，128.3，128.0，127.6，124.3，123.6，122.0，116.8，115.6，62.2，28.8；ESI-MS m/z 321.0[M+H]+.As described in method A, 4-(benzyloxy)-N-(2-iodophenyl)-N-methyl-2-butyneamide (1.0 mmol) was mixed with NaN 3 (1.2 mmol), K 2 CO 3 (2.0mmol), CuI (0.05mmol), ligand 2-pyridinecarboxylic acid or 2-pyrrolecarboxylic acid (0.1mmol) in DMSO (1mL), stirred at 90°C for 6h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 234 mg of white solid, yield: 73%; 1 H NMR (CDCl 3 , 400MHz) δ8.55 (dd, J=8.8Hz, J =1.6Hz, 1H), 7.59(td, J=8.0Hz, J=1.2Hz, 1H), 7.41-7.45(m, 4H), 7.33(t, J=7.6Hz, 2H), 7.24-7.28(m , 1H), 5.11(s, 3H), 4.74(s, 2H), 3.72(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.0, 145.8, 138.0, 130.2, 129.5, 128.3, 128.0, 127.6, 124.3, 123.6, 122.0, 116.8, 115.6, 62.2, 28.8; ESI-MS m/z 321.0[M+H] + .
实施例21Example 21
按照如方法A所述，N-(2-碘-4-甲氧基苯)-N-甲基-3-苯丙炔酰胺(1.0mmol)与NaN3(2.0mmol)、K3PO4(2.0mmol)，CuBr(0.15mmol)，配体N，N-二甲基甘氨酸盐酸盐或8-羟基喹啉(0.5mmol)在DMSO(1mL)中40℃搅拌40h。粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体223mg，产率：73％；1H NMR(CDCl3，400MHz)δ8.36(d，J＝7.2Hz，2H)，8.07(d，J＝2.8Hz，1H)，7.52(t，J＝7.2Hz，2H)，7.45(t，J＝7.2Hz，1H)，7.36(d，J＝9.2Hz，1H)，7.16(dd，J＝9.2Hz，J＝2.8Hz，1H)，3.97(s，3H)，3.73(s，3H)；13C NMR(CDCl3，125MHz)δ156.4，153.8，148.6，129.4，129.3，128.3，123.9，122.7，121.9，117.4，116.8，100.3，56.1，29.2；ESI-MS m/z 307.1[M+H]+.N-(2-iodo-4-methoxybenzene)-N-methyl-3-phenylpropynamide (1.0 mmol) was mixed with NaN 3 (2.0 mmol), K 3 PO 4 ( 2.0 mmol), CuBr (0.15 mmol), ligand N, N-dimethylglycine hydrochloride or 8-hydroxyquinoline (0.5 mmol) were stirred in DMSO (1 mL) at 40° C. for 40 h. The crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 223 mg of white solid, yield: 73%; 1 H NMR (CDCl 3 , 400 MHz) δ8.36 (d, J=7.2 Hz, 2H ), 8.07(d, J=2.8Hz, 1H), 7.52(t, J=7.2Hz, 2H), 7.45(t, J=7.2Hz, 1H), 7.36(d, J=9.2Hz, 1H), 7.16(dd, J=9.2Hz, J=2.8Hz, 1H), 3.97(s, 3H), 3.73(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ156.4, 153.8, 148.6, 129.4, 129.3, 128.3, 123.9, 122.7, 121.9, 117.4, 116.8, 100.3, 56.1, 29.2; ESI-MS m/z 307.1[M+H] + .
实施例22Example 22
底物I(X＝Br)与NaN3的反应(方法B)Reaction of Substrate I (X=Br) with NaN 3 (Method B)
在一个一端密封的反应管内，加入N-(2-溴苯基)-N-甲基-2-丁炔酰胺(1.0mmol)，然后加入NaN3(1.1mmol)，CuI(0.15mmol)，1.0ml DMSO作为溶剂，在氩气或氮气保护下，于90℃搅拌反应20h，用10毫升水稀释反应混合液，有大量固体析出，过滤，滤液用10毫升乙酸乙酯萃取两次，合并有机相，干燥后减压旋干得淡黄色固体，将所得固体和滤饼合并柱层析(淋洗液石油醚∶乙酸乙酯＝10∶1)得产物188mg，产率88％；1H NMR(CDCl3，400MHz)δ8.50(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.58(td，J＝8.0Hz，J＝1.2Hz，1H)，7.39-7.42(m，2H)，3.70(s，3H)，2.80(s，3H)；13C NMR(CDCl3，125MHz)δ154.8，130.3，129.2，124.1，122.4，116.7，115.6，28.6，11.4；ESI-MS m/z 215.1[M+H]+.In a reaction tube sealed at one end, N-(2-bromophenyl)-N-methyl-2-butynamide (1.0mmol) was added, followed by NaN 3 (1.1mmol), CuI (0.15mmol), 1.0 ml DMSO as a solvent, under the protection of argon or nitrogen, stir the reaction at 90°C for 20 h, dilute the reaction mixture with 10 ml of water, a large amount of solid precipitates, filter, and extract the filtrate twice with 10 ml of ethyl acetate, combine the organic phase , dried and spin-dried under reduced pressure to obtain a light yellow solid, and the resulting solid and filter cake were combined for column chromatography (eluent petroleum ether: ethyl acetate = 10:1) to obtain 188 mg of the product, with a yield of 88%; 1 H NMR ( CDCl 3 , 400MHz) δ8.50(dd, J=8.8Hz, J=1.6Hz, 1H), 7.58(td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42(m, 2H), 3.70(s, 3H), 2.80(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.8, 130.3, 129.2, 124.1, 122.4, 116.7, 115.6, 28.6, 11.4; ESI-MS m/z 215.1 [M+H] + .
实施例23Example 23
在一个一端密封的反应管内，加入N-(2-溴4-甲氧羰基苯基)-N-甲基-2-丁炔酰胺(1.0mmol)，然后加入NaN3(1.1mmol)，CuI(0.15mmol)，1.0ml DMSO作为溶剂，在氩气或氮气保护下，于90℃搅拌反应20h，用10毫升水稀释反应混合液，有大量固体析出，过滤，滤液用10毫升乙酸乙酯萃取两次，合并有机相，干燥后减压旋干得淡黄色固体，将所得固体和滤饼合并柱层析(淋洗液石油醚∶乙酸乙酯＝10∶1)得产物246mg，产率90％；1H NMR(CDCl3，400MHz)δ8.50(s，1H)，7.78(d，J＝8.0Hz，1H)，7.39(d，J＝8.0Hz，1H)，4.12(s，3H)，3.77(s，3H)，2.83(s，3H)；13C NMR(CDCl3，125MHz)δ167.4，154.8，135.3，133.2，127.1，125.4，118.7，117.6，61.2，30.6，12.4；ESI-MS m/z 273.1[M+H]+.In a reaction tube sealed at one end, N-(2-bromo4-methoxycarbonylphenyl)-N-methyl-2-butynamide (1.0mmol) was added, followed by NaN 3 (1.1mmol), CuI( 0.15mmol), 1.0ml DMSO was used as a solvent, under the protection of argon or nitrogen, stirred at 90°C for 20h, diluted the reaction mixture with 10ml of water, a large amount of solids were precipitated, filtered, and the filtrate was extracted with 10ml of ethyl acetate. Once, the organic phases were combined, dried and spin-dried under reduced pressure to obtain a light yellow solid, and the resulting solid and filter cake were combined for column chromatography (eluent petroleum ether: ethyl acetate=10: 1) to obtain 246 mg of product, yield 90% ; 1 H NMR (CDCl 3 , 400MHz) δ8.50(s, 1H), 7.78(d, J=8.0Hz, 1H), 7.39(d, J=8.0Hz, 1H), 4.12(s, 3H), 3.77(s, 3H), 2.83(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ167.4, 154.8, 135.3, 133.2, 127.1, 125.4, 118.7, 117.6, 61.2, 30.6, 12.4; ESI-MS m/z 273.1[M+H] + .
实施例24Example 24
按照如方法B所述，N-(2-溴苯基)-N-甲基-3-苯丙炔酰胺(1.0mmol)与NaN3(1.1mmol)CuI(0.15mmol)，1.0ml DMF作为溶剂，在氩气或氮气保护下，于90℃搅拌反应20h，粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体224mg，产率：81％；1H NMR(CDCl3，400MHz)δ8.60(dd，J＝8.4Hz，J＝1.6Hz，1H)，8.36(d，J＝7.2Hz，2H)，7.61(td，J＝8.0Hz，J＝1.6Hz，1H)，7.50-7.54(m，2H)，7.43-7.47(m，3H)，3.75(s，3H)；13C NMR(CDCl3，125MHz)δ154.3，148.6，130.2，129.4，129.3，128.3，124.2，122.2，121.6，116.9，115.5，29.1；ESI-MS m/z 277.1[M+H]+.N-(2-bromophenyl)-N-methyl-3-phenylpropynamide (1.0 mmol) and NaN3 (1.1 mmol) CuI (0.15 mmol), 1.0 ml DMF as solvent as described in method B , under the protection of argon or nitrogen, stirred and reacted at 90°C for 20h, the crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 224 mg of white solid, yield: 81%; 1 H NMR (CDCl 3 , 400MHz) δ8.60(dd, J=8.4Hz, J=1.6Hz, 1H), 8.36(d, J=7.2Hz, 2H), 7.61(td, J=8.0Hz, J=1.6Hz, 1H ), 7.50-7.54 (m, 2H), 7.43-7.47 (m, 3H), 3.75 (s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.3, 148.6, 130.2, 129.4, 129.3, 128.3, 124.2, 122.2, 121.6, 116.9, 115.5, 29.1; ESI-MS m/z 277.1[M+H] + .
实施例25Example 25
按照如方法B所述，N-(2-溴苯基)-N-甲基-2-己炔酰胺(1.0mmol)与NaN3(1.5mmol)，CuI(0.05mmol)在DMSO(1mL)中，90℃搅拌反应20h，粗产物经柱层析(3∶1二氯甲烷∶石油醚)提纯得白色固体211mg，产率：87％；1H NMR(CDCl3，400MHz)δ8.51(d，J＝8.0Hz，1H)，7.56(td，J＝8.0Hz，J＝1.2Hz，1H)，7.39-7.42(m，2H)，3.70(s，3H)，3.17(t，J＝8.0Hz，2H)，1.83-1.90(m，2H)，1.03(t，J＝7.2Hz，3H)；13C NMR(CDCl3，125MHz)δ154.7，130.3，129.1，124.0，122.4，116.7，115.5，28.6，27.6，22.7，13.8；ESI-MS m/z 243.3[M+H]+.N-(2-Bromophenyl)-N-methyl-2-hexynamide (1.0 mmol) with NaN3 (1.5 mmol), CuI (0.05 mmol) in DMSO (1 mL) as described in Method B , stirred and reacted at 90°C for 20h, the crude product was purified by column chromatography (3:1 dichloromethane:petroleum ether) to obtain 211 mg of white solid, yield: 87%; 1 H NMR (CDCl 3 , 400MHz) δ8.51(d , J=8.0Hz, 1H), 7.56(td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42(m, 2H), 3.70(s, 3H), 3.17(t, J=8.0Hz , 2H), 1.83-1.90 (m, 2H), 1.03 (t, J=7.2Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.7, 130.3, 129.1, 124.0, 122.4, 116.7, 115.5, 28.6, 27.6, 22.7, 13.8; ESI-MS m/z 243.3[M+H] + .
实施例26Example 26
底物I(X＝Cl)与NaN3的反应(方法C)Reaction of Substrate I (X=Cl) with NaN 3 (Method C)
在一个一端密封的反应管内，加入N-(2-氯苯基)-N-甲基-2-丁炔酰胺(1.0mmol)，然后加入NaN3(1.5mmol)，K2CO3(2mmol)，L-脯氨酸(0.2mmol)，CuI(0.1mmol)，1.0ml DMF作为溶剂，在氩气或氮气保护下，于110℃搅拌反应10h，用10毫升水稀释反应混合液，有大量固体析出，过滤，滤液用10毫升乙酸乙酯萃取两次，合并有机相，干燥后减压旋干得淡黄色固体，将所得固体和滤饼合并柱层析(淋洗液石油醚∶乙酸乙酯＝10∶1)得产物154mg，产率72％；1H NMR(CDCl3，400MHz)δ8.50(dd，J＝8.8Hz，J＝1.6Hz，1H)，7.58(td，J＝8.0Hz，J＝1.2Hz，1H)，7.39-7.42(m，2H)，3.70(s，3H)，2.80(s，3H)；13C NMR(CDCl3，125MHz)δ154.8，130.3，129.2，124.1，122.4，116.7，115.6，28.6，11.4；ESI-MS m/z 215.1[M+H]+.In a reaction tube sealed at one end, N-(2-chlorophenyl)-N-methyl-2-butynamide (1.0 mmol) was added, followed by NaN 3 (1.5 mmol), K 2 CO 3 (2 mmol) , L-proline (0.2mmol), CuI (0.1mmol), 1.0ml DMF as a solvent, under the protection of argon or nitrogen, stirred and reacted at 110°C for 10h, diluted the reaction mixture with 10ml of water, there were a lot of solids Precipitated, filtered, and the filtrate was extracted twice with 10 milliliters of ethyl acetate, the organic phases were combined, dried and spin-dried under reduced pressure to obtain a light yellow solid, and the resulting solid and filter cake were combined for column chromatography (eluent petroleum ether: ethyl acetate =10:1) to obtain 154 mg of product, yield 72%; 1 H NMR (CDCl 3 , 400MHz) δ8.50 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.58 (td, J=8.0Hz , J=1.2Hz, 1H), 7.39-7.42(m, 2H), 3.70(s, 3H), 2.80(s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.8, 130.3, 129.2, 124.1 , 122.4, 116.7, 115.6, 28.6, 11.4; ESI-MS m/z 215.1[M+H] + .
实施例27Example 27
按照如方法C所述，N-(2-氯苯基)-N-甲基-3-苯丙炔酰胺(1.0mmol)与NaN3(1.5mmol)，CuSO4(0.5mmol)，配体L-脯氨酸或4-羟基脯氨酸(1mmol)在DMSO(1mL)中110℃搅拌反应10h，得黄色固体168mg产率：61％；1H NMR(CDCl3，400MHz)δ8.60(dd，J＝8.4Hz，J＝1.6Hz，1H)，8.36(d，J＝7.2Hz，2H)，7.61(td，J＝8.0Hz，J＝1.6Hz，1H)，7.50-7.54(m，2H)，7.43-7.47(m，3H)，3.75(s，3H)；13C NMR(CDCl3，125MHz)δ154.3，148.6，130.2，129.4，129.3，128.3，124.2，122.2，121.6，116.9，115.5，29.1；ESI-MS m/z 277.1[M+H]+.As described in method C, N-(2-chlorophenyl)-N-methyl-3-phenylpropynamide (1.0 mmol) with NaN 3 (1.5 mmol), CuSO 4 (0.5 mmol), ligand L -Proline or 4-hydroxyproline (1mmol) was stirred in DMSO (1mL) at 110°C for 10h to obtain 168mg of yellow solid. Yield: 61%; 1 H NMR (CDCl 3 , 400MHz) δ8.60(dd , J=8.4Hz, J=1.6Hz, 1H), 8.36(d, J=7.2Hz, 2H), 7.61(td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54(m, 2H ), 7.43-7.47 (m, 3H), 3.75 (s, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.3, 148.6, 130.2, 129.4, 129.3, 128.3, 124.2, 122.2, 121.6, 116.9, 115.5 , 29.1; ESI-MS m/z 277.1[M+H] + .
实施例28Example 28
按照方法C所述，N-(2-碘苯基)-N-甲基-2-庚炔酰胺(1.0mmol)与NaN3(1.5mmol)，CuI(0.2mmol)，L-脯氨酸(0.4mmol)在DMF(1mL)中150℃搅拌反应10h在得黄色固体148mg产率：58％；1H NMR(CDCl3，400MHz)δ8.50(d，J＝7.6Hz，1H)，7.56(td，J＝8.0Hz，J＝1.2Hz，1H)，7.38-7.42(m，2H)，3.70(s，3H)，3.19(t，J＝8.0Hz，2H)，1.78-1.86(m，2H)，1.40-1.50(m，2H)，0.98(t，J＝4.8Hz，3H)；13C NMR(CDCl3，125MHz)δ154.7，150.6，130.3，129.1，124.0，122.3，122.2，116.7，115.5，31.4，28.6，25.4，22.4，13.8；ESI-MS m/z 257.1[M+H]+。N-(2-iodophenyl)-N-methyl-2-heptyneamide (1.0 mmol) was mixed with NaN3 (1.5 mmol), CuI (0.2 mmol), L-proline ( 0.4 mmol) was stirred in DMF (1 mL) at 150°C for 10 h to obtain 148 mg of a yellow solid. Yield: 58%; 1 H NMR (CDCl 3 , 400 MHz) δ8.50 (d, J=7.6 Hz, 1H), 7.56 ( td, J=8.0Hz, J=1.2Hz, 1H), 7.38-7.42(m, 2H), 3.70(s, 3H), 3.19(t, J=8.0Hz, 2H), 1.78-1.86(m, 2H ), 1.40-1.50 (m, 2H), 0.98 (t, J=4.8Hz, 3H); 13 C NMR (CDCl 3 , 125MHz) δ154.7, 150.6, 130.3, 129.1, 124.0, 122.3, 122.2, 116.7, 115.5, 31.4, 28.6, 25.4, 22.4, 13.8; ESI-MS m/z 257.1 [M+H] + .
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| JP2016124812A (en) * | 2014-12-26 | 2016-07-11 | 株式会社ヤクルト本社 | Compound having znf143 inhibitory activity and use thereof |
| CN107602570A (en) * | 2017-10-24 | 2018-01-19 | 暨南大学 | A kind of nitrogenous polynary and heterocyclic compound method of synthesis |
| CN114195792A (en) * | 2021-12-03 | 2022-03-18 | 常州大学 | A kind of synthetic method of 1,2,3-triazole quinoxalinone derivatives |
| CN115321495A (en) * | 2022-07-28 | 2022-11-11 | 东北石油大学 | A kind of synthetic method of metal nitrogen-rich compound FeN8 |
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| SU721441A1 (en) * | 1977-11-17 | 1980-03-15 | Пермский государственный фармацевтический институт | Method of preparing 1,2,3-triazolo-(1,5-a) quinoxalone-4 |
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| JP2016124812A (en) * | 2014-12-26 | 2016-07-11 | 株式会社ヤクルト本社 | Compound having znf143 inhibitory activity and use thereof |
| CN107602570A (en) * | 2017-10-24 | 2018-01-19 | 暨南大学 | A kind of nitrogenous polynary and heterocyclic compound method of synthesis |
| CN114195792A (en) * | 2021-12-03 | 2022-03-18 | 常州大学 | A kind of synthetic method of 1,2,3-triazole quinoxalinone derivatives |
| CN115321495A (en) * | 2022-07-28 | 2022-11-11 | 东北石油大学 | A kind of synthetic method of metal nitrogen-rich compound FeN8 |
| CN115321495B (en) * | 2022-07-28 | 2023-07-21 | 东北石油大学 | A kind of synthetic method of metal nitrogen-rich compound FeN8 |
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