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US 2003/0119899 A1Published application
Process and intermediates for making substituted aspartic acid acetals
AssigneeVertex Pharmaceuticals Incorporated
InventorsMarion W. Wannamaker, Cornelia Forster
Life of this patent
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Abstract
Disclosed herein is a method for making compounds that are useful as caspase inhibitor prodrugs of formula I: 1 wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is preferably a P2-P4 moiety of a caspase inhibitor. Key intermediates include the azidolactones III and VIII: 2
Claims34
A process for making a compound of formula I:
- 144
- wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is an organic radical, said process comprising the steps of:
- (a) providing a butenolactone of formula II:
- 145
- (b) treating II with an azide N3—Y, where Y is hydrogen, a silyl group, or a counterion, to form an azidolactone III:
- 146
- (c) converting III to an aminolactone IV or an iminophosphorane V:
- 147
- and
- (d) coupling either IV or V with R2COOH, or a reactive equivalent thereof, to form I.
7 more elements
A process for making a compound of formula I:
- 148
- wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is an organic radical, said process comprising the steps of:
- (a) providing a butenolactone VII:
- 149
- where X is chloro, bromo or iodo;
- (b) treating VII with an azide N3—Y, where Y is a silyl group or a counterion, to form the azidobutenolactone VIII:
- 150
- (c) converting VIII to an aminobutenolactone IX or an iminophosphorane XI:
- 151
- (d) coupling either IX or XI with R2COOH, or a reactive equivalent thereof, to form X:
- 152
- (e) reducing the furanone ring double bond in X to provide I.
9 more elements
A process for making a compound of formula I:
- 153
- wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is an organic radical, said process comprising the steps of:
- (a) providing a butenolactone VII:
- 154
- wherein X is chloro, bromo or iodo;
- (b) treating VII with an azide N3—Y, where Y is a silyl group or a counterion, to form an azidobutenolactone VIII:
- 155
- (c) converting VIII to an aminobutenolactone IX:
- 156
- (d) reducing the ring double bond of IX to provide the aminolactone IV:
- 157
- and
- (e) coupling IV with R2COOH, or a reactive equivalent thereof, to form I.
10 more elements
A compound of formula III or VIII:
- 158
- wherein R1 is selected from an optionally substituted aliphatic group, aralkyl group or aryl group.
A compound of formula V or IX:
- 159
- wherein R1 is selected from an optionally substituted aliphatic group, aralkyl group or aryl group.
Dependencies are inferred from the claim text.