HRP960079A2 - Process for the preparation of diltiazem - Google Patents
Process for the preparation of diltiazem Download PDFInfo
- Publication number
- HRP960079A2 HRP960079A2 HR950719A HRP960079A HRP960079A2 HR P960079 A2 HRP960079 A2 HR P960079A2 HR 950719 A HR950719 A HR 950719A HR P960079 A HRP960079 A HR P960079A HR P960079 A2 HRP960079 A2 HR P960079A2
- Authority
- HR
- Croatia
- Prior art keywords
- toluene
- mixture
- image
- reaction
- methylpyrrolidin
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 30
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 title claims description 9
- 229960004166 diltiazem Drugs 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 68
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 13
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 9
- 238000004821 distillation Methods 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000007126 N-alkylation reaction Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- -1 sodium metal amide Chemical class 0.000 description 3
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- RBNIRJMBLFRIEM-UHFFFAOYSA-N n,3-dichloro-n-methylpropan-1-amine Chemical compound CN(Cl)CCCCl RBNIRJMBLFRIEM-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Vascular Medicine (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI950719A FI97725C (fi) | 1995-02-17 | 1995-02-17 | Menetelmä diltiatseemin valmistamiseksi |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960079A2 true HRP960079A2 (en) | 1997-10-31 |
Family
ID=8542879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR950719A HRP960079A2 (en) | 1995-02-17 | 1996-02-16 | Process for the preparation of diltiazem |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5644054A (bs) |
| EP (1) | EP0728751A3 (bs) |
| JP (1) | JPH08253464A (bs) |
| BA (1) | BA96073A (bs) |
| CA (1) | CA2169717A1 (bs) |
| CZ (1) | CZ287706B6 (bs) |
| EE (1) | EE9600007A (bs) |
| FI (1) | FI97725C (bs) |
| HR (1) | HRP960079A2 (bs) |
| HU (1) | HU218609B (bs) |
| IL (1) | IL117084A (bs) |
| LV (1) | LV11466B (bs) |
| PL (1) | PL312826A1 (bs) |
| RU (1) | RU2139853C1 (bs) |
| SI (1) | SI9600051A (bs) |
| SK (1) | SK20696A3 (bs) |
| YU (1) | YU8996A (bs) |
| ZA (1) | ZA961120B (bs) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3033701B1 (fr) | 2015-03-19 | 2021-01-15 | Univ Claude Bernard Lyon | Nouvelles compositions antivirales pour le traitement de la grippe |
| US12594280B2 (en) | 2015-03-19 | 2026-04-07 | Universite Claude Bernard Lyon 1 | Antiviral compositions for treating the flu |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3582257A (en) * | 1968-05-10 | 1971-06-01 | Monsanto Co | Soil and stain resistance and soil and stain release properties in textile articles |
| JPS5899471A (ja) * | 1981-12-07 | 1983-06-13 | Tanabe Seiyaku Co Ltd | ベンゾチアゼピン誘導体の新規製造法 |
| SE449611B (sv) * | 1982-07-09 | 1987-05-11 | Tanabe Seiyaku Co | Sett att framstella 1,5-bensotiazepinderivat |
| FR2624117B1 (fr) * | 1987-12-08 | 1991-02-22 | Synthelabo | Derives de hydroxy-3 (methoxy-4 phenyl)-2 (methylamino-2 ethyl)-5 dihydro-2,3 5h-benzothiazepine-1,5 one-4, leur preparation et leur application en therapeutique |
| FR2630109B1 (fr) * | 1988-04-19 | 1991-11-29 | Synthelabo | Derives de ((n-(amino-2 oxo-2 ethyl)methylamino)-2 ethyl)-5 hydroxy-3 (methoxy-4 phenyl)-2 dihydro-2,3 5h-benzothiazepine-1,5 one-4, leur preparation et leur application en therapeutique |
| US4908469A (en) * | 1988-05-18 | 1990-03-13 | Marion Laboratories, Inc. | 2-Hydroxy-propanoic acid acyclic alkyl esters for benzothiazepines |
| US5002942A (en) * | 1988-07-25 | 1991-03-26 | Sankyo Company, Limited | 1,5-benzothiazepine derivatives, their preparation and their use in the treatment of cardiovascular disorders |
| FR2653122B1 (fr) * | 1989-10-17 | 1994-04-15 | Synthelabo | Derives de 5-[2-[[2-amino-2-oxoethyl]methylamino]ethyl]-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5(5h)-benzothiazepine-4-one, leur preparation et leur application en therapeutique. |
| IT1240686B (it) * | 1990-04-27 | 1993-12-17 | Luso Farmaco Inst | Derivati 1,5-benzotiazepinonici, loro preparazione e uso farmaceutico |
| IT1244878B (it) * | 1990-12-11 | 1994-09-12 | Lusochimica Spa | Processo per la preparazione del (+)-cis-3-(acetossi)-5-!2-( dimetilammino)etil!-2,3-diidro-2-(4-metossifenil)-1,5-benzotiazepin- 4-(5h)-one cloridrato |
| IT1255545B (it) * | 1992-10-23 | 1995-11-09 | Procedimento per la preparazione di diltiazem | |
| FI93741C (fi) * | 1993-03-24 | 1995-05-26 | Orion Yhtymae Oy | Menetelmä optisesti puhtaitten (2S,3S)- ja (2R,3R)-threo-alkyyli-2-hydroksi-3-(4-metoksifenyyli)-3-(2-X-fenyylitio)propionaattien tai vastaavien asyloitujen yhdisteiden valmistamiseksi |
-
1995
- 1995-02-17 FI FI950719A patent/FI97725C/fi active
-
1996
- 1996-02-08 IL IL11708496A patent/IL117084A/xx not_active IP Right Cessation
- 1996-02-12 ZA ZA961120A patent/ZA961120B/xx unknown
- 1996-02-14 US US08/601,182 patent/US5644054A/en not_active Expired - Fee Related
- 1996-02-15 PL PL96312826A patent/PL312826A1/xx unknown
- 1996-02-15 SK SK206-96A patent/SK20696A3/sk unknown
- 1996-02-15 EE EE9600007A patent/EE9600007A/xx unknown
- 1996-02-15 CZ CZ1996454A patent/CZ287706B6/cs not_active IP Right Cessation
- 1996-02-16 BA BA960073A patent/BA96073A/bs unknown
- 1996-02-16 RU RU96102864A patent/RU2139853C1/ru active
- 1996-02-16 JP JP8029609A patent/JPH08253464A/ja active Pending
- 1996-02-16 HR HR950719A patent/HRP960079A2/hr not_active Application Discontinuation
- 1996-02-16 SI SI9600051A patent/SI9600051A/sl unknown
- 1996-02-16 YU YU8996A patent/YU8996A/sh unknown
- 1996-02-16 EP EP96102348A patent/EP0728751A3/en not_active Ceased
- 1996-02-16 CA CA002169717A patent/CA2169717A1/en not_active Abandoned
- 1996-02-16 HU HU9700350A patent/HU218609B/hu not_active IP Right Cessation
- 1996-02-16 LV LVP-96-47A patent/LV11466B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CZ287706B6 (en) | 2001-01-17 |
| LV11466A (lv) | 1996-08-20 |
| BA96073A (bs) | 2001-09-14 |
| SI9600051A (en) | 1996-08-31 |
| EP0728751A3 (en) | 1996-10-23 |
| YU8996A (sh) | 1998-08-14 |
| IL117084A (en) | 2001-03-19 |
| CA2169717A1 (en) | 1996-08-18 |
| FI950719L (fi) | 1996-08-18 |
| HU218609B (hu) | 2000-10-28 |
| FI950719A0 (fi) | 1995-02-17 |
| LV11466B (en) | 1996-12-20 |
| CZ45496A3 (en) | 1996-09-11 |
| PL312826A1 (en) | 1996-08-19 |
| FI97725C (fi) | 1997-02-10 |
| RU2139853C1 (ru) | 1999-10-20 |
| ZA961120B (en) | 1996-08-20 |
| EP0728751A2 (en) | 1996-08-28 |
| US5644054A (en) | 1997-07-01 |
| IL117084A0 (en) | 1996-06-18 |
| HU9600350D0 (en) | 1996-04-29 |
| EE9600007A (et) | 1996-10-15 |
| FI97725B (fi) | 1996-10-31 |
| SK20696A3 (en) | 1997-05-07 |
| JPH08253464A (ja) | 1996-10-01 |
| HUP9600350A1 (en) | 1997-04-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| ODBI | Application refused |