US3959253A
Expired / Lapsed
US
⏱️ 0.0 years remaining
β-D-glucosyluronic acid derivatives
Assignee: Merck and Co Inc
•
Filing: 1973-07-02
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Granted: 1976-05-25
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Expires: 1993-07-02
Abstract
Abstract Process for preparing β-D-glucosyluronic acid derivatives of pharmaceutical acids by the controlled hydrolysis of the corresponding 2,3,4-tri-O-acyl β-D-glucopyranosidyl uronate esters of the free acids.
Inventors
- 👤 Howard Jones
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 17:21
CPC Classifications
C; C07; C07H; C07H13/00; C07H13/02; C07H13/08
Claims Analysis
Total Claims: 8
Claim 1
Independent Claim
86 words
A process for preparing 1-O-β-D-glucopyranosyluronic acid ester of: a. 5-fluoro-2-methy-1-(p-methylsulfinylbenzylidene) indenyl-3-acetic acid; b. 5-fluoro-2-methyl-1-(p-methylsulfonylbenzylidene) indenyl-3-acetic acid; c. 5-methoxy-2-methyl-1-(p-chlorobenzylidene)-indenyl-3-acetic acid; d. 4-amino-2-hydroxybenzoic acid; e. 2-hydroxybenzoic acid; f. p-(dipropylsulfamoyl) benzoic acid; g. [2,3-dichloro-4-(2-methylenebutynyl)phenoxy] -acetic acid; h. pyridine-3-carboxylic acid; or i. trans-4-(aminomethyl) cyclohexanecarboxylic acid; which comprises hydrolyzing the corresponding 2,3,4-tri-O-acetyl-1-O-βD-glucopyranosyluronate esters in a polar solvent in the presence of an acid, wherein the mole ratio of acid to ester starting material is about 4 to 15, and the normality of the total reaction mixture is between 0.5 and 1.5.
Claim 2
Dependent Claim
86 words
A process for preparing 1-O-β-D-glucopyranosyluronic acid ester of: a. 5-fluoro-2-methy-1-(p-methylsulfinylbenzylidene) indenyl-3-acetic acid; b. 5-fluoro-2-methyl-1-(p-methylsulfonylbenzylidene) indenyl-3-acetic acid; c. 5-methoxy-2-methyl-1-(p-chlorobenzylidene)-indenyl-3-acetic acid; d. 4-amino-2-hydroxybenzoic acid; e. 2-hydroxybenzoic acid; f. p-(dipropylsulfamoyl) benzoic acid; g. [2,3-dichloro-4-(2-methylenebutynyl)phenoxy] -acetic acid; h. pyridine-3-carboxylic acid; or i. trans-4-(aminomethyl) cyclohexanecarboxylic acid; which comprises hydrolyzing the corresponding 2,3,4-tri-O-acetyl-1-O-βD-glucopyranosyluronate esters in a polar solvent in the presence of an acid, wherein the mole ratio of acid to ester starting material is about 4 to 15, and the normality of the total reaction mixture is between 0.5 and 1.5.
Claim 3
Dependent Claim
40 words
The process of claim 1 wherein the mole ratio is about 6 to about 9, the normality of the reaction mixture is between about 0.6 to about 1.0 and the temperature of reaction is between about 60°C to about 100°C.
Claim 4
Dependent Claim
15 words
The process of claim 1 wherein the uronate ester is the 2,3,4-tri-C 1-5 alkyl ester.
Claim 5
Dependent Claim
22 words
The process of claim 2 wherein the uronate ester is selected from the group consisting of methyl-[5-fluoro-2-methyl-1-(p-methylsulfinylbenzylidene)-indenyl-3-acetyl]-2,3,4-tri-O-acetyl-β-D-glucopyranosidyl uronate or methyl-[5-fluoro-2-methyl-1-(p-methylsulfonylbenzylidene)-indenyl-3acetyl]-2,3,4-tri-o-acetyl-β -D-glucopyranosidyl uronate.
Claim 6
Dependent Claim
28 words
The process of claim 2 wherein the polar solvent is selected from the group consisting of an ether, C 1-5 alkanol, C 1-3 alkylamide or di-C 2-6 alkylsulfoxide.
Claim 7
Dependent Claim
33 words
A compound selected from the group consisting of the β-D-glucopyrosidyluronic acids of [5-fluoro-2-methyl-1-(p-methylsulfinylbenzylidene)-indenyl-3-acetic acid, 5-fluoro-2-methyl-1-(p-methylsulfonylbenzylidene)-indenyl-3-acetic acid,] 5-methoxy-2-methyl-1-(p-chlorobenzylidene)-indenyl-3-acetic acid, 4-amino-2-hydroxybenzoic acid, o-hydroxybenzoic acid, p-(dipropylsulfamoyl)benzoic acid, (2,3-dichloro-4-(2-methylenebutynyl)-phenoxy) acetic acid, pyridine-3-carboxylic acid or trans-4-(aminomethyl)-cyclohexane carboxylic acid.
Claim 8
Dependent Claim
33 words
A compound selected from the group consisting of the β-D-glucopyrosidyluronic acids of [5-fluoro-2-methyl-1-(p-methylsulfinylbenzylidene)-indenyl-3-acetic acid, 5-fluoro-2-methyl-1-(p-methylsulfonylbenzylidene)-indenyl-3-acetic acid,] 5-methoxy-2-methyl-1-(p-chlorobenzylidene)-indenyl-3-acetic acid, 4-amino-2-hydroxybenzoic acid, o-hydroxybenzoic acid, p-(dipropylsulfamoyl)benzoic acid, (2,3-dichloro-4-(2-methylenebutynyl)-phenoxy) acetic acid, pyridine-3-carboxylic acid or trans-4-(aminomethyl)-cyclohexane carboxylic acid.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-05-25 | 1979-11-24 | 1980-05-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-05-25 | 1983-11-24 | 1984-05-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-05-25 | 1987-11-24 | 1988-05-25 | $7700.00 | Window Closed / Lapsed |