RU2557241C1 - Способ синтеза фторклозапина и его производных - Google Patents

Способ синтеза фторклозапина и его производных Download PDF

Info

Publication number: RU2557241C1
Authority: RU; Russia
Prior art keywords: formula; compound; atom; solvent; optionally substituted
Prior art date: 2014-07-31

Application number

RU2014131750/04A

Other languages

English (en)

Russian (ru)

Inventor

Максим Эдуардович Запольский

Маргарита Алексеевна Морозова

Аллан Герович Бениашвили

Original Assignee

Общество с ограниченной ответственностью "Валентек" (ООО "Валентек")

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2014-07-31

Filing date

2014-07-31

Publication date

2015-07-20

2014-07-31 Application filed by Общество с ограниченной ответственностью "Валентек" (ООО "Валентек") filed Critical Общество с ограниченной ответственностью "Валентек" (ООО "Валентек")

2014-07-31 Priority to RU2014131750/04A priority Critical patent/RU2557241C1/ru

2014-12-12 Priority to CN201480080814.9A priority patent/CN106573917A/zh

2014-12-12 Priority to PCT/RU2014/000940 priority patent/WO2016018173A1/fr

2015-07-20 Application granted granted Critical

2015-07-20 Publication of RU2557241C1 publication Critical patent/RU2557241C1/ru

Links

238000000034 method Methods 0.000 title claims abstract description 26
230000015572 biosynthetic process Effects 0.000 title description 15
238000003786 synthesis reaction Methods 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims abstract description 94
239000002904 solvent Substances 0.000 claims abstract description 22
UIOYEIHBWQTVJC-UHFFFAOYSA-N 1-chloro-2,4-difluoro-5-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=C(F)C=C1F UIOYEIHBWQTVJC-UHFFFAOYSA-N 0.000 claims abstract description 11
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims abstract description 7
150000001412 amines Chemical class 0.000 claims abstract description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 14
239000011541 reaction mixture Substances 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
230000009467 reduction Effects 0.000 claims description 9
-1 Ν-methylpyrrolidone Chemical compound 0.000 claims description 9
230000003993 interaction Effects 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 8
125000004434 sulfur atom Chemical group 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
238000007363 ring formation reaction Methods 0.000 claims description 7
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
238000002425 crystallisation Methods 0.000 claims description 4
230000008025 crystallization Effects 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 3
239000000010 aprotic solvent Substances 0.000 claims description 3
238000010438 heat treatment Methods 0.000 claims description 3
239000003880 polar aprotic solvent Substances 0.000 claims description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
239000000126 substance Substances 0.000 abstract description 4
230000000694 effects Effects 0.000 abstract description 2
238000006798 ring closing metathesis reaction Methods 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
239000012535 impurity Substances 0.000 description 14
239000000047 product Substances 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 7
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238000009835 boiling Methods 0.000 description 5
235000019441 ethanol Nutrition 0.000 description 5
239000000725 suspension Substances 0.000 description 5
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
229960004170 clozapine Drugs 0.000 description 4
125000003963 dichloro group Chemical group Cl* 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000011261 inert gas Substances 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
OYDFCTWDAVIWPU-UHFFFAOYSA-N C=1(SC2=C(C=1)C(=NC1=CC(=C(F)C=C1N2)Cl)N)C Chemical compound C=1(SC2=C(C=1)C(=NC1=CC(=C(F)C=C1N2)Cl)N)C OYDFCTWDAVIWPU-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 3
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
JUDKQDCBSOLCIA-UHFFFAOYSA-N 2-(2-amino-4-chloro-5-fluoroanilino)-5-methylthiophene-3-carbonitrile Chemical compound NC1=C(C=C(C(=C1)Cl)F)NC=1SC(=CC=1C#N)C JUDKQDCBSOLCIA-UHFFFAOYSA-N 0.000 description 2
AFSIVWIJVLQNOT-UHFFFAOYSA-N 7-chloro-8-fluoro-2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine Chemical compound C=1(SC2=C(C(=NC3=CC(=C(F)C=C3N2)Cl)N2CCN(CC2)C)C=1)C AFSIVWIJVLQNOT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
239000000164 antipsychotic agent Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000012467 final product Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
208000020016 psychiatric disease Diseases 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
YIKBHZYACWVCOX-UHFFFAOYSA-N 2-(4-chloro-5-fluoro-2-nitroanilino)-5-methylthiophene-3-carbonitrile Chemical compound CC1=CC(=C(S1)NC1=C(C=C(C(=C1)F)Cl)[N+](=O)[O-])C#N YIKBHZYACWVCOX-UHFFFAOYSA-N 0.000 description 1
QRJHCRVSZBZGNT-UHFFFAOYSA-N 2-[2-[4-(3-chloro-2-fluoro-11H-benzo[b][1,4]benzodiazepin-6-yl)piperazin-1-yl]ethoxy]ethanol Chemical compound N1C2=C(C(=NC3=CC(=C(F)C=C13)Cl)N1CCN(CC1)CCOCCO)C=CC=C2 QRJHCRVSZBZGNT-UHFFFAOYSA-N 0.000 description 1
YGXADLPRHBRTPG-UHFFFAOYSA-N 2-amino-5-methylthiophene-3-carbonitrile Chemical compound CC1=CC(C#N)=C(N)S1 YGXADLPRHBRTPG-UHFFFAOYSA-N 0.000 description 1
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WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
DYKRALKWGIWCPV-UHFFFAOYSA-N C1=CC=C2C(=C1)C(=NC3=CC(=C(C=C3N2)F)Cl)N.Cl Chemical compound C1=CC=C2C(=C1)C(=NC3=CC(=C(C=C3N2)F)Cl)N.Cl DYKRALKWGIWCPV-UHFFFAOYSA-N 0.000 description 1
CHZXBGDWPYVNEV-UHFFFAOYSA-N C1=CC=C2C(=C1)C=NNC3=C2C(=C(C=C3)Cl)Cl Chemical compound C1=CC=C2C(=C1)C=NNC3=C2C(=C(C=C3)Cl)Cl CHZXBGDWPYVNEV-UHFFFAOYSA-N 0.000 description 1
GUJLRSVWNBPSNE-UHFFFAOYSA-N Cc1cc(C(NCl)=Nc(c(N2)c3)cc(Cl)c3F)c2[s]1 Chemical compound Cc1cc(C(NCl)=Nc(c(N2)c3)cc(Cl)c3F)c2[s]1 GUJLRSVWNBPSNE-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
QSIYSUHKCZVIDB-UHFFFAOYSA-N N#Cc(cccc1)c1Nc(cc(c(Cl)c1)F)c1[N+]([O-])=O Chemical compound N#Cc(cccc1)c1Nc(cc(c(Cl)c1)F)c1[N+]([O-])=O QSIYSUHKCZVIDB-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
YPQHXZUZJLGKGK-UHFFFAOYSA-N Nc(cc(c([N+]([O-])=O)c1)N)c1N Chemical compound Nc(cc(c([N+]([O-])=O)c1)N)c1N YPQHXZUZJLGKGK-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
QOTAEASRCGCJDN-UHFFFAOYSA-N [C].CO Chemical class [C].CO QOTAEASRCGCJDN-UHFFFAOYSA-N 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000000295 fuel oil Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000005457 ice water Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
230000004630 mental health Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
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239000004576 sand Substances 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
239000007858 starting material Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000005406 washing Methods 0.000 description 1

Images

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

RU2014131750/04A 2014-07-31 2014-07-31 Способ синтеза фторклозапина и его производных RU2557241C1 (ru)

Priority Applications (3)

Application Number	Priority Date	Filing Date	Title
RU2014131750/04A RU2557241C1 (ru)	2014-07-31	2014-07-31	Способ синтеза фторклозапина и его производных
CN201480080814.9A CN106573917A (zh)	2014-07-31	2014-12-12	合成氟氯氮平及其衍生物的方法
PCT/RU2014/000940 WO2016018173A1 (fr)	2014-07-31	2014-12-12	Procédé de synthèse de fluoro clozapine et de ses dérivés

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
RU2014131750/04A RU2557241C1 (ru)	2014-07-31	2014-07-31	Способ синтеза фторклозапина и его производных

Publications (1)

Publication Number	Publication Date
RU2557241C1 true RU2557241C1 (ru)	2015-07-20

Family

ID=53611748

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
RU2014131750/04A RU2557241C1 (ru)	2014-07-31	2014-07-31	Способ синтеза фторклозапина и его производных

Country Status (3)

Country	Link
CN (1)	CN106573917A (fr)
RU (1)	RU2557241C1 (fr)
WO (1)	WO2016018173A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2667954C2 (ru) *	2016-03-04	2018-09-25	Общество С Ограниченной Ответственностью "Валентек"	Фармацевтическая композиция для лечения функциональных психических расстройств
CN111718302A (zh) *	2020-06-15	2020-09-29	江苏慈星药业有限公司	一种氯氮平中间体及其合成方法和应用

Citations (3)

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WO2016018173A1 (fr)	2016-02-04

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