CN103804294B - Synthetic method of 7 or 9-chloro-4,5-dihydro-1hydro-benzo[b]azepine-2(3hydro)-one - Google Patents
Synthetic method of 7 or 9-chloro-4,5-dihydro-1hydro-benzo[b]azepine-2(3hydro)-one Download PDFInfo
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- CN103804294B CN103804294B CN201410035968.8A CN201410035968A CN103804294B CN 103804294 B CN103804294 B CN 103804294B CN 201410035968 A CN201410035968 A CN 201410035968A CN 103804294 B CN103804294 B CN 103804294B
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- China
- Prior art keywords
- hydrogen
- chloro
- benzo
- dihydro
- azatropylidene
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 17
- 239000012074 organic phase Substances 0.000 claims description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 14
- BLNVISNJTIRAHF-UHFFFAOYSA-N 4-chlorobenzamide Chemical compound NC(=O)C1=CC=C(Cl)C=C1 BLNVISNJTIRAHF-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 9
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 238000005727 Friedel-Crafts reaction Methods 0.000 claims description 5
- 239000008346 aqueous phase Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 239000012266 salt solution Substances 0.000 claims description 5
- 238000006856 Wolf-Kishner-Huang Minlon reduction reaction Methods 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 238000000746 purification Methods 0.000 abstract description 3
- 238000007363 ring formation reaction Methods 0.000 abstract description 3
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 229910000510 noble metal Inorganic materials 0.000 abstract description 2
- 238000006722 reduction reaction Methods 0.000 abstract description 2
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 abstract 1
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 abstract 1
- 238000006898 Intramolecular Friedel-Crafts reaction Methods 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 229940014800 succinic anhydride Drugs 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- UPSNSRKMOHOEEO-UHFFFAOYSA-N 4-(4-chloroanilino)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC1=CC=C(Cl)C=C1 UPSNSRKMOHOEEO-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000005649 metathesis reaction Methods 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- RZPFVRFSYMUDJO-UHFFFAOYSA-N 2h-naphthalen-1-one Chemical compound C1=CC=C2C(=O)CC=CC2=C1 RZPFVRFSYMUDJO-UHFFFAOYSA-N 0.000 description 1
- GWHPLVIIGOTUJS-UHFFFAOYSA-N 4-(2-chloroanilino)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC1=CC=CC=C1Cl GWHPLVIIGOTUJS-UHFFFAOYSA-N 0.000 description 1
- 238000006237 Beckmann rearrangement reaction Methods 0.000 description 1
- RREGPCQVUJXAFB-UHFFFAOYSA-N CC(CC(c1cc(Cl)ccc1N1)=O)C1=O Chemical compound CC(CC(c1cc(Cl)ccc1N1)=O)C1=O RREGPCQVUJXAFB-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
- WXZRWXDXKODMJY-UHFFFAOYSA-N O=C(CCC1)Nc(cc2)c1cc2Cl Chemical compound O=C(CCC1)Nc(cc2)c1cc2Cl WXZRWXDXKODMJY-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000005865 alkene metathesis reaction Methods 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000011984 grubbs catalyst Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NPSSWQJHYLDCNV-UHFFFAOYSA-N prop-2-enoic acid;hydrochloride Chemical compound Cl.OC(=O)C=C NPSSWQJHYLDCNV-UHFFFAOYSA-N 0.000 description 1
- WLHPCEJPGLYEJZ-UHFFFAOYSA-N prop-2-enyltin Chemical compound [Sn]CC=C WLHPCEJPGLYEJZ-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 108010064245 urinary gonadotropin fragment Proteins 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410035968.8A CN103804294B (en) | 2014-01-24 | 2014-01-24 | Synthetic method of 7 or 9-chloro-4,5-dihydro-1hydro-benzo[b]azepine-2(3hydro)-one |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410035968.8A CN103804294B (en) | 2014-01-24 | 2014-01-24 | Synthetic method of 7 or 9-chloro-4,5-dihydro-1hydro-benzo[b]azepine-2(3hydro)-one |
Publications (2)
Publication Number | Publication Date |
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CN103804294A CN103804294A (en) | 2014-05-21 |
CN103804294B true CN103804294B (en) | 2015-04-01 |
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CN201410035968.8A Active CN103804294B (en) | 2014-01-24 | 2014-01-24 | Synthetic method of 7 or 9-chloro-4,5-dihydro-1hydro-benzo[b]azepine-2(3hydro)-one |
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CN (1) | CN103804294B (en) |
Families Citing this family (2)
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CN109400533A (en) * | 2018-11-07 | 2019-03-01 | 亳州学院 | A kind of synthetic method of hydrochloric acid conivaptan key intermediate |
CN113636977B (en) * | 2021-09-01 | 2022-12-20 | 温州大学 | Synthesis method of 2-aryl benzazepine and derivatives thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102174016A (en) * | 2011-03-02 | 2011-09-07 | 宁波人健药业集团有限公司 | Method for preparing 7-chloro-2,3,4,5-tetrahydro-1H-1-benzoazepine-2,5-diketone |
CN103288709A (en) * | 2013-05-17 | 2013-09-11 | 安徽世华化工有限公司 | Synthesis method of 5-fluorine-indol-2-ketone |
-
2014
- 2014-01-24 CN CN201410035968.8A patent/CN103804294B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102174016A (en) * | 2011-03-02 | 2011-09-07 | 宁波人健药业集团有限公司 | Method for preparing 7-chloro-2,3,4,5-tetrahydro-1H-1-benzoazepine-2,5-diketone |
CN103288709A (en) * | 2013-05-17 | 2013-09-11 | 安徽世华化工有限公司 | Synthesis method of 5-fluorine-indol-2-ketone |
Non-Patent Citations (2)
Title |
---|
"A Facile Synthesis of 1,3,4,6-Tetrahydro-1,6-benzodiazocine-2,5-diones";D.V. Jarikote等;《Russian Journal of Organic Chemistry》;20041231;第40卷(第4期);第575页Scheme1 * |
"Synthesis of Tetrahydrobenzazepinesulfonamides and Their Rearrangement to Diarylsulfones";Hui Hui等;《Synthetic Communications》;20061231(第36期);第357页Scheme1 * |
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CN103804294A (en) | 2014-05-21 |
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C06 | Publication | ||
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C10 | Entry into substantive examination | ||
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C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20150922 Address after: Wenjiang District 611130 of Sichuan city of Chengdu province Chengdu Strait science and Technology Industry Development Park No. 488 West Ke Lin Lu Patentee after: ASTATECH (CHENGDU) PHARM. CO., LTD. Address before: High tech Zone Gaopeng road in Chengdu city of Sichuan province in 610041 No. 5 students Pioneering Park East (Chengdu) Medical Technology Co Ltd Patentee before: AstaTech (Chengdu) Pharmaceutical Co., Ltd. |
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C56 | Change in the name or address of the patentee | ||
CP03 | Change of name, title or address |
Address after: Wenjiang District 610000 of Sichuan city of Chengdu province Chengdu Strait science and Technology Industry Development Park No. 488 West Ke Lin Lu Patentee after: Astatech (Chengdu) biological pharmaceutical Limited by Share Ltd Address before: Wenjiang District 611130 of Sichuan city of Chengdu province Chengdu Strait science and Technology Industry Development Park No. 488 West Ke Lin Lu Patentee before: ASTATECH (CHENGDU) PHARM. CO., LTD. |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Synthetic method of 7 or 9-chloro-4,5-dihydro-1hydro-benzo[b]azepine-2(3hydro)-one Effective date of registration: 20170822 Granted publication date: 20150401 Pledgee: Chengdu SME financing Company Limited by Guarantee Pledgor: Astatech (Chengdu) biological pharmaceutical Limited by Share Ltd Registration number: 2017510000052 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20180801 Granted publication date: 20150401 Pledgee: Chengdu SME financing Company Limited by Guarantee Pledgor: Astatech (Chengdu) biological pharmaceutical Limited by Share Ltd Registration number: 2017510000052 |
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PC01 | Cancellation of the registration of the contract for pledge of patent right |