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US4438035A
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Method of preparing benzothiazepine derivatives
Assignee: Tanabe Pharma Corp
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Filing: 1982-12-01
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Granted: 1984-03-20
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Expires: 2002-12-01
Abstract
Abstract A benzothiazepine derivative of the formula: ##STR1## wherein R is hydrogen or acetyl, is prepared by condensing a compound of the formula: ##STR2## wherein R is the same as defined above, with 2-(diamethylamino)ethyl halide (i) in the presence of potassium hydroxide in acetone; or (ii) in the presence of potassium carbonate in acetone, lower alkyl acetate, a mixture of acetone and water or a mixture of lower alkyl acetate and water.
Inventors
- 👤 Mitsunori Gaino
- 👤 Ikuo Iijima
- 👤 Shigeru Nishimoto
- 👤 Kuichiro Ikeda
- 👤 Tokuo Fujii
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 17:46
CPC Classifications
C; C07; C07D; C07D281/00; C07D281/02; C07D281/04; C07D281/08; C07D281/10; A; A61; A61P; A61P9/00; A61P9/08; A61P9/10
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
100 words
A method of preparing a benzothiazepine derivative of the formula: ##STR5## wherein R is hydrogen or acetyl, or a pharmaceutically acceptable acid addition salt thereof, which comprises condensing a compound of the formula: ##STR6## wherein R is the same as defined above, with 2-(dimethylamino)ethyl halide either in the presence of potassium hydroxide in acetone or in the presence of potassium carbonate in a solvent selected from acetone, lower alkyl acetate, a mixture of acetone and water and a mixture of lower alkyl acetate and water, and if required, further converting the product into a pharmaceutically acceptable acid addition salt thereof.
Claim 2
Independent Claim
100 words
A method of preparing a benzothiazepine derivative of the formula: ##STR5## wherein R is hydrogen or acetyl, or a pharmaceutically acceptable acid addition salt thereof, which comprises condensing a compound of the formula: ##STR6## wherein R is the same as defined above, with 2-(dimethylamino)ethyl halide either in the presence of potassium hydroxide in acetone or in the presence of potassium carbonate in a solvent selected from acetone, lower alkyl acetate, a mixture of acetone and water and a mixture of lower alkyl acetate and water, and if required, further converting the product into a pharmaceutically acceptable acid addition salt thereof.
Claim 3
Dependent Claim
100 words
The method according to claim 1, wherein the condensation is carried out either in the presence of 1 to 3 moles of potassium hydroxide per mole of the compound (II) in acetone at a temperature between 30° C. and the refluxing temperature of acetone or in the presence of 1 to 5 moles of potassium carbonate per mole of the compound (II) in a solvent selected from acetone, lower alkyl acetate, a mixture of acetone and water and a mixture of lower alkyl acetate and water at a temperature of 30° C. and the refluxing temperature of the solvent used.
Claim 4
Dependent Claim
132 words
The method according to claim 1, wherein, when potassium hydroxide and acetone are used, the condensation is carried out by stirring a mixture of the compound (II), 2-(dimethylamino)ethyl chloride, potassium hydroxide and acetone at a temperature of 40° C. to 57° C.; when potassium carbonate and acetone or lower alkyl acetate are used, the condensation is carried out by refluxing a mixture of the compound (II), 2-(dimethylamino)ethyl chloride, potassium carbonate and acetone or lower alkyl acetate; when potassium carbonate and a mixture of acetone and water or a mixture of lower alkyl acetate and water are used, the condensation is carried out by refluxing a mixture of the compound (II), 2-(dimethylamino)ethyl chloride, potassium carbonate and acetone or lower alkyl acetate, adding water to the mixture and then further refluxing the aqueous mixture.
Claim 5
Dependent Claim
17 words
The method according to claim 1, wherein the lower alkyl acetate is methyl acetate or ethyl acetate.
Claim 6
Dependent Claim
17 words
The method according to claim 3, wherein the lower alkyl acetate is methyl acetate or ethyl acetate.
Claim 7
Dependent Claim
17 words
The method according to claim 3, wherein 2-(dimethylamino)ethyl chloride is used in the form of its hydrochloride.
Claim 8
Dependent Claim
40 words
The method according to claim 6, wherein the amount of potassium hydroxide is 2 to 2.5 moles per mole of the compound (II), and the amount of potassium carbonate is 2 to 3 moles per mole of the compound (II).
Claim 9
Dependent Claim
132 words
The method according to claim 2, wherein, when potassium hydroxide and acetone are used, the condensation is carried out by stirring a mixture of the compound (II), 2-(dimethylamino)ethyl chloride, potassium hydroxide and acetone at a temperature of 40° C. to 57° C.; when potassium carbonate and acetone or lower alkyl acetate are used, the condensation is carried out by refluxing a mixture of the compound (II), 2-(dimethylamino)ethyl chloride, potassium carbonate and acetone or lower alkyl acetate; when potassium carbonate and a mixture of acetone and water or a mixture of lower alkyl acetate and water are used, the condensation is carried out by refluxing a mixture of the compound (II), 2-(dimethylamino)ethyl chloride, potassium carbonate and acetone or lower alkyl acetate, adding water to the mixture and then further refluxing the aqueous mixture.
Claim 10
Dependent Claim
17 words
The method according to claim 2, wherein the lower alkyl acetate is methyl acetate or ethyl acetate.
Claim 11
Dependent Claim
17 words
The method according to claim 8, wherein the lower alkyl acetate is methyl acetate or ethyl acetate.
Claim 12
Dependent Claim
17 words
The method according to claim 8, wherein 2-(dimethylamino)ethyl chloride is used in the form of its hydrochloride.
Claim 13
Dependent Claim
40 words
The method according to claim 11, wherein the amount of potassium hydroxide is 2 to 2.5 moles per mole of the compound (II), and the amount of potassium carbonate is 2 to 3 moles per mole of the compound (II).
References Cited (Backward Citations)
US3562257A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-03-20 | 1987-09-19 | 1988-03-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-03-20 | 1991-09-19 | 1992-03-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-03-20 | 1995-09-19 | 1996-03-20 | $7700.00 | Window Closed / Lapsed |