IL107246A - Process for the preparation of diltiazem - Google Patents

Process for the preparation of diltiazem

Info

Publication number: IL107246A
Authority: IL; Israel
Prior art keywords: formula; toluene; iii; process according; solvent
Prior art date: 1992-10-23

Application number

IL10724693A

Other languages

English (en)

Other versions

IL107246A0 (en

Original Assignee

Profarmaco S R L

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.)

1992-10-23

Filing date

1993-10-11

Publication date

1999-11-30

1993-10-11 Application filed by Profarmaco S R L filed Critical Profarmaco S R L

1994-01-25 Publication of IL107246A0 publication Critical patent/IL107246A0/xx

1999-11-30 Publication of IL107246A publication Critical patent/IL107246A/en

Links

238000000034 method Methods 0.000 title claims abstract description 21
238000002360 preparation method Methods 0.000 title claims abstract description 9
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 abstract description 10
229960004166 diltiazem Drugs 0.000 title abstract description 10
239000002904 solvent Substances 0.000 claims abstract description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 70
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 10
150000001875 compounds Chemical class 0.000 claims description 9
239000003849 aromatic solvent Substances 0.000 claims description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 claims description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
239000008096 xylene Substances 0.000 claims description 3
OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
230000000397 acetylating effect Effects 0.000 claims description 2
229940117389 dichlorobenzene Drugs 0.000 claims description 2
125000003944 tolyl group Chemical group 0.000 claims description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
150000008041 alkali metal carbonates Chemical class 0.000 claims 1
FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical compound S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 abstract 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 8
239000000203 mixture Substances 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
239000000243 solution Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
239000002585 base Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
239000000047 product Substances 0.000 description 3
238000011084 recovery Methods 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
238000004891 communication Methods 0.000 description 2
238000010908 decantation Methods 0.000 description 2
230000007613 environmental effect Effects 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
238000005406 washing Methods 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-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
206010002383 Angina Pectoris Diseases 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
101100260565 Dictyostelium discoideum thyA gene Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
LSHMSPDFIQJBFK-UHFFFAOYSA-N [N].S1N=CC=CC=C1 Chemical compound [N].S1N=CC=CC=C1 LSHMSPDFIQJBFK-UHFFFAOYSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
-1 alkyl acetate Chemical compound 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000000480 calcium channel blocker Substances 0.000 description 1
239000007806 chemical reaction intermediate Substances 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
238000004821 distillation Methods 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 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
238000000926 separation method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
101150068774 thyX gene Proteins 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Urology & Nephrology (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)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Steroid Compounds (AREA)

IL10724693A 1992-10-23 1993-10-11 Process for the preparation of diltiazem IL107246A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
ITMI922432A IT1255545B (it)	1992-10-23	1992-10-23	Procedimento per la preparazione di diltiazem

Publications (2)

Publication Number	Publication Date
IL107246A0 IL107246A0 (en)	1994-01-25
IL107246A true IL107246A (en)	1999-11-30

Family

ID=11364158

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10724693A IL107246A (en)	1992-10-23	1993-10-11	Process for the preparation of diltiazem

Country Status (8)

Country	Link
US (1)	US5495013A (de)
EP (1)	EP0594101B1 (de)
JP (1)	JP3531954B2 (de)
AT (1)	ATE146785T1 (de)
CA (1)	CA2108950A1 (de)
DE (1)	DE69306908T2 (de)
IL (1)	IL107246A (de)
IT (1)	IT1255545B (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2576690B2 (ja) *	1993-03-11	1997-01-29	日本電気株式会社	ディジタル携帯電話機
FI97725C (fi) *	1995-02-17	1997-02-10	Orion Yhtymae Oy	Menetelmä diltiatseemin valmistamiseksi
TW438787B (en) *	1997-02-27	2001-06-07	Tanabe Seiyaku Co	Process for preparing optically active trans-3-substituted glycidic acid ester
CN103305583A (zh) *	2012-03-12	2013-09-18	江苏华荣生物科技有限公司	简便化提取消旋对甲氧苯基缩水甘油酸甲酯

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3562257A (en) *	1967-10-28	1971-02-09	Tanabe Seiyaku Co	Benzothiazepine derivatives
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
US4902684A (en) *	1988-06-20	1990-02-20	E. R. Squibb & Sons, Inc.	Benzazepine and benzothiazepine derivatives
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
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

1992
- 1992-10-23 IT ITMI922432A patent/IT1255545B/it active IP Right Grant
1993
- 1993-10-11 IL IL10724693A patent/IL107246A/en not_active IP Right Cessation
- 1993-10-18 AT AT93116782T patent/ATE146785T1/de active
- 1993-10-18 EP EP93116782A patent/EP0594101B1/de not_active Expired - Lifetime
- 1993-10-18 DE DE69306908T patent/DE69306908T2/de not_active Expired - Fee Related
- 1993-10-21 JP JP28563593A patent/JP3531954B2/ja not_active Expired - Fee Related
- 1993-10-21 CA CA002108950A patent/CA2108950A1/en not_active Abandoned
1994
- 1994-10-20 US US08/326,312 patent/US5495013A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
ITMI922432A1 (it)	1994-04-23
IL107246A0 (en)	1994-01-25
JPH06228117A (ja)	1994-08-16
EP0594101A1 (de)	1994-04-27
JP3531954B2 (ja)	2004-05-31
IT1255545B (it)	1995-11-09
ATE146785T1 (de)	1997-01-15
DE69306908D1 (de)	1997-02-06
CA2108950A1 (en)	1994-04-24
DE69306908T2 (de)	1997-05-07
ITMI922432A0 (it)	1992-10-23
US5495013A (en)	1996-02-27
EP0594101B1 (de)	1996-12-27

Legal Events

Date	Code	Title
2000-06-01	FF	Patent granted
2000-08-31	KB	Patent renewed
2004-01-04	KB	Patent renewed
2008-08-10	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0098892B1 (de)	1987-10-28	Verfahren zur Herstellung von 1,5-Benzothiazepin-Derivaten
EP4284778B1 (de)	2025-12-17	Verfahren zur herstellung von levetiracetam und zwischenprodukten davon
EP0325965B1 (de)	1994-04-13	Verfahren zur optischen Spaltung einer rakemischen Säure
EP0405524B1 (de)	1993-11-03	Verfahren zur Reinigung von Tryptophan
EP0561861B1 (de)	1995-03-22	Verfahren zur herstellung von diltiazem
IL107246A (en)	1999-11-30	Process for the preparation of diltiazem
US4566995A (en)	1986-01-28	Process for the preparation of benzothiazepine derivatives
EP0702009B1 (de)	1998-07-01	Verfahren zur Herstellung von pharmazeutisch aktiven Benzothiazepinderivaten.
CA2589699A1 (en)	2006-06-15	Process for the preparation of carvedilol and its enantiomers
US4239885A (en)	1980-12-16	Process for the preparation of diacetone acrylamide
US4360696A (en)	1982-11-23	Process for the preparation of diacetone acrylamide
US4864058A (en)	1989-09-05	Process for making optically active naphtho[1,2-b][1,4]thiazepin-4(5H)-ones
RU2139853C1 (ru)	1999-10-20	Способ получения дилтиазема
US4996352A (en)	1991-02-26	Enantiomers of β-[(2-amino-1-naphthalenyl) thiol]-α-hydroxy-4-methoxybenzene propanoic acid
CA1284321C (en)	1991-05-21	Process for preparing benzothiazepine derivatives
US5225557A (en)	1993-07-06	Process for making optically active naphtho[1,2-b]thiazepin-4(5H)-ones
RU2098412C1 (ru)	1997-12-10	Способ получения гидрохлорида этилового эфира 10-(3-диэтиламинопропионил)фенотиазинкарбаминовой-2 кислоты
KR860000781B1 (ko)	1986-06-25	1,5-벤조티아제핀 유도체의 제조방법
FI93009C (fi)	1995-02-10	Menetelmä 1,5-bentsotiatsepiinijohdannaisten valmistamiseksi
HK95588A (en)	1988-12-02	Process for preparing 1,5-benzothiazepine derivatives
WO1996038429A1 (en)	1996-12-05	Method for the manufacture of benzothiazepine derivatives
GB2328208A (en)	1999-02-17	Resolution of alpha-propionic acids