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US4298744A Expired / Lapsed US ⏱️ 0.0 years remaining

Method for preparing (αS,5S)-α-amino-3-chloro-2-isoxazoline-5-acetic acid (AT-125) and analogs thereof

Assignee: Pharmacia and Upjohn Co
•
Filing: 1979-07-13
•
Granted: 1981-11-03
•
Expires: 1999-07-13
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Abstract

Abstract Chemical process for preparing AT-125 and its analogs and intermediates used in the process.

Inventors

  • 👤 Robert C. Kelly
  • 👤 Wendell Wierenga

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-26 04:07
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/44; C07D209/48; C07C; C07C247/00; C07D261/00; C07D261/02; C07D261/04; C07D303/00; C07D303/02; C07D303/04

Claims Analysis

Total Claims: 13
Claim 1
Independent Claim 264 words
A process for preparing racemic mixtures and optically active isomers of a compound having the formula ##STR86## which comprises chlorinating a compound having the formula ##STR87## wherein R is selected from the group consisting of hydrogen, alkyl of from 1 to 8 carbon atoms, inclusive, halogenated alkyl of from 1 to 3 halogen atoms, and 1 to 5 carbon atoms, inclusive and aralkyl of from 7 to 20 carbon atoms, inclusive and substituted aralkyl of from 7 to 20 carbon atoms, inclusive; and R 14 and R 15 are selected from the group consisting of hydrogen, ##STR88## inclusive, or when taken together with the nitrogen atom form the group ##STR89## wherein R 6 is alkyl of from 1 to 8 carbon atoms, inclusive, halogenated alkyl of from 1 to 5 carbon atoms, inclusive, and 1 to 3 halogen atoms, inclusive, aralkyl of from 7 to 20 carbon atoms, inclusive, and substituted aralkyl of from 7 to 20 carbon atoms, inclusive, R 7 is selected from the group consisting of alkyl of from 1 to 12 carbon atoms, inclusive, aryl of from 6 to 20 carbon atoms, inclusive, aryl of from 6 to 20 carbon atoms, inclusive, aralkyl of from 7 to 20 carbon atoms, inclusive, substituted aralkyl of from 7 to 20 carbon atoms, inclusive, and R 8 is selected from the group consisting of ##STR90## where R 9 , R 10 , R 11 and R 12 are selected from the group consisting of hydrogen and alkyl of from 1 to 5 carbon atoms, inclusive, (b) ##STR91## (c) orthointerphenylene, and (d) substituted orthointerphenylene.
Claim 2
Dependent Claim 264 words
A process for preparing racemic mixtures and optically active isomers of a compound having the formula ##STR86## which comprises chlorinating a compound having the formula ##STR87## wherein R is selected from the group consisting of hydrogen, alkyl of from 1 to 8 carbon atoms, inclusive, halogenated alkyl of from 1 to 3 halogen atoms, and 1 to 5 carbon atoms, inclusive and aralkyl of from 7 to 20 carbon atoms, inclusive and substituted aralkyl of from 7 to 20 carbon atoms, inclusive; and R 14 and R 15 are selected from the group consisting of hydrogen, ##STR88## inclusive, or when taken together with the nitrogen atom form the group ##STR89## wherein R 6 is alkyl of from 1 to 8 carbon atoms, inclusive, halogenated alkyl of from 1 to 5 carbon atoms, inclusive, and 1 to 3 halogen atoms, inclusive, aralkyl of from 7 to 20 carbon atoms, inclusive, and substituted aralkyl of from 7 to 20 carbon atoms, inclusive, R 7 is selected from the group consisting of alkyl of from 1 to 12 carbon atoms, inclusive, aryl of from 6 to 20 carbon atoms, inclusive, aryl of from 6 to 20 carbon atoms, inclusive, aralkyl of from 7 to 20 carbon atoms, inclusive, substituted aralkyl of from 7 to 20 carbon atoms, inclusive, and R 8 is selected from the group consisting of ##STR90## where R 9 , R 10 , R 11 and R 12 are selected from the group consisting of hydrogen and alkyl of from 1 to 5 carbon atoms, inclusive, (b) ##STR91## (c) orthointerphenylene, and (d) substituted orthointerphenylene.
Claim 3
Dependent Claim 34 words
A process according to claim 1 wherein the compound prepared has the formula ##STR92## and the compound chlorinated has the formula ##STR93## wherein R and R 8 are the same as in claim 1.
Claim 4
Dependent Claim 11 words
A process according to claim 2 wherein R 8 is orthointerphenylene.
Claim 5
Dependent Claim 21 words
A process according to claim 3 wherein R is benzhydryl so that the compound prepared is (αS,5S)-chloro-4,5-dihydro-α-phthalimido-5-isoxazole acetic acid, benzhydryl ester.
Claim 6
Dependent Claim 31 words
A process according to claim 1 wherein the compound prepared has the formula ##STR94## and the compound chlorinated has the formula ##STR95## wherein R is the same as in claim 1.
Claim 7
Dependent Claim 19 words
A process according to claim 5 wherein R is hydrogen so that the compound prepared is (αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid.
Claim 8
Dependent Claim 27 words
A process according to claim 3 wherein R is methyl and R 8 is orthointerphenylene, so that the compound prepared is phthalyl (αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid methyl ester.
Claim 9
Dependent Claim 23 words
A process according to claim 2 or 7 wherein the chlorinating agent comprises carbon tetrachloride and hexamethylphosphorous in the presence of a solvent.
Claim 10
Dependent Claim 16 words
A process according to claim 2 or 7 wherein the chlorinating agent comprises hexamethylphosphorous triamide dichloride.
Claim 11
Dependent Claim 15 words
A process according to claim 5 or 6 wherein the chlorinating agent comprises phosphorous oxychloride.
Claim 12
Dependent Claim 24 words
A process according to claim 1 wherein the compound prepared is optionally treated with hydrogen bromide to yield a compound having the formula ##STR96##
Claim 13
Dependent Claim 23 words
A process according to claim 4 wherein the compound prepared is optionally treated with hydrogen bromide to yield (αS,5S)-bromo-4,5-dihydro-α-phthalimido-5-isoxazole acetic acid benzhydryl ester.

References Cited (Backward Citations)

US3856807A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1984-11-02 1985-05-04 1985-11-03 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1988-11-02 1989-05-04 1989-11-03 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1992-11-02 1993-05-04 1993-11-03 $7700.00 Window Closed / Lapsed

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