DE2504937A1 - Verfahren zur herstellung von benzodiazepinderivaten - Google Patents
Verfahren zur herstellung von benzodiazepinderivatenInfo
- Publication number
- DE2504937A1 DE2504937A1 DE19752504937 DE2504937A DE2504937A1 DE 2504937 A1 DE2504937 A1 DE 2504937A1 DE 19752504937 DE19752504937 DE 19752504937 DE 2504937 A DE2504937 A DE 2504937A DE 2504937 A1 DE2504937 A1 DE 2504937A1
- Authority
- DE
- Germany
- Prior art keywords
- radical
- formula
- group
- compound
- hydrogen
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 22
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title claims description 4
- 150000001557 benzodiazepines Chemical class 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title description 5
- -1 alkanoyl radical Chemical class 0.000 claims description 33
- 150000001875 compounds Chemical class 0.000 claims description 22
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 claims description 12
- 229960001454 nitrazepam Drugs 0.000 claims description 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 239000004215 Carbon black (E152) Substances 0.000 claims description 9
- 229930195733 hydrocarbon Natural products 0.000 claims description 9
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 8
- 150000003254 radicals Chemical class 0.000 claims description 7
- 229960003529 diazepam Drugs 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000002466 imines Chemical class 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 claims 2
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000006798 ring closing metathesis reaction Methods 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- QLNAVQRIWDRPHA-UHFFFAOYSA-N iminophosphane Chemical compound P=N QLNAVQRIWDRPHA-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 150000003003 phosphines Chemical class 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- CPLWKNRPZVNELG-UHFFFAOYSA-N (3-chlorophenyl)-phenylmethanone Chemical class ClC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 CPLWKNRPZVNELG-UHFFFAOYSA-N 0.000 description 2
- MFYLRNKOXORIPK-UHFFFAOYSA-N (3-nitrophenyl)-phenylmethanone Chemical class [O-][N+](=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 MFYLRNKOXORIPK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical group COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/22—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/28—Preparation including building-up the benzodiazepine skeleton from compounds containing no hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NLAANVRAGE7401801,A NL162379C (nl) | 1974-02-08 | 1974-02-08 | Werkwijze ter bereiding van benzodiazepinederivaten. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2504937A1 true DE2504937A1 (de) | 1975-08-14 |
Family
ID=19820720
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752504937 Withdrawn DE2504937A1 (de) | 1974-02-08 | 1975-02-06 | Verfahren zur herstellung von benzodiazepinderivaten |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS50112389A (OSRAM) |
| BE (1) | BE825300A (OSRAM) |
| DE (1) | DE2504937A1 (OSRAM) |
| DK (1) | DK39775A (OSRAM) |
| FR (1) | FR2260580A1 (OSRAM) |
| IL (1) | IL46575A0 (OSRAM) |
| IN (1) | IN138664B (OSRAM) |
| NL (1) | NL162379C (OSRAM) |
| NO (1) | NO750400L (OSRAM) |
| ZA (1) | ZA75713B (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4395409A (en) * | 1980-06-04 | 1983-07-26 | Hoechst Aktiengesellschaft | Carbamoyloxyamino-1,4-benzodiazepines and medicaments containing these compounds |
| CN115304554A (zh) * | 2022-09-19 | 2022-11-08 | 公安部物证鉴定中心 | 一种2’-氯地西泮-d3的制备方法 |
-
1974
- 1974-02-08 NL NLAANVRAGE7401801,A patent/NL162379C/xx not_active IP Right Cessation
-
1975
- 1975-02-04 ZA ZA00750713A patent/ZA75713B/xx unknown
- 1975-02-05 IL IL46575A patent/IL46575A0/xx unknown
- 1975-02-06 DK DK39775*#A patent/DK39775A/da unknown
- 1975-02-06 DE DE19752504937 patent/DE2504937A1/de not_active Withdrawn
- 1975-02-07 IN IN225/CAL/75A patent/IN138664B/en unknown
- 1975-02-07 FR FR7503963A patent/FR2260580A1/fr active Granted
- 1975-02-07 BE BE153162A patent/BE825300A/xx unknown
- 1975-02-07 NO NO750400A patent/NO750400L/no unknown
- 1975-02-08 JP JP50015912A patent/JPS50112389A/ja active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4395409A (en) * | 1980-06-04 | 1983-07-26 | Hoechst Aktiengesellschaft | Carbamoyloxyamino-1,4-benzodiazepines and medicaments containing these compounds |
| CN115304554A (zh) * | 2022-09-19 | 2022-11-08 | 公安部物证鉴定中心 | 一种2’-氯地西泮-d3的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| BE825300A (nl) | 1975-08-07 |
| IL46575A0 (en) | 1975-04-25 |
| NL162379B (nl) | 1979-12-17 |
| IN138664B (OSRAM) | 1976-03-13 |
| NL162379C (nl) | 1984-07-16 |
| DK39775A (OSRAM) | 1975-09-29 |
| NO750400L (OSRAM) | 1975-09-01 |
| FR2260580A1 (en) | 1975-09-05 |
| NL7401801A (nl) | 1975-08-12 |
| JPS50112389A (OSRAM) | 1975-09-03 |
| ZA75713B (en) | 1976-01-28 |
| FR2260580B3 (OSRAM) | 1977-10-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8141 | Disposal/no request for examination |