SYNTHESIS OF PYRROLIDINE COMPOUNDS

摘要

Provided are methods for the preparation of certain substituted pyrrolidine compounds, forms of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride, and methods for preparing and using these forms.

主权项

1. A method for preparing a compound of formula (I) or a salt thereof:wherein:
one of Wand R2 is hydrogen or C1-C6 alkyl, and the other is —C(O)R5;
wherein R5 is chosen from:
optionally substituted C6-C10 aryl;optionally substituted heteroaryl including 5-10 atoms;optionally substituted C1-C20 alkyl;optionally substituted C1-C20 haloalkyl;optionally substituted C7-C12 aralkyl;optionally substituted heteroaralkyl including 6-12 atoms;optionally substituted C3-C10 cycloalkyl; andoptionally substituted C3-C10 cycloalkenyl; W is C1-6 alkylene; and R3 and R4 may be the same or different and are each independently chosen from hydrogen, optionally substituted C1-C6 alkyl, —C(O)OR6, and —C(O)R9;
wherein R6 is optionally substituted C1-C20 alkyl; andwherein R9 is chosen from
hydrogen;optionally substituted C6-C10 aryl;optionally substituted heteroaryl including 5-10 atoms;optionally substituted C1-C20 alkyl;optionally substituted C3-C10 cycloalkyl; andoptionally substituted heterocycloalkyl including 5-10 atoms;the method comprising:
converting a compound of formula (II) or a salt thereof:wherein:
R7 is chosen from hydrogen and optionally substituted C1-C6 alkyl;to a compound of formula (III) or a salt thereof:and, where R7 in formula (III) is optionally substituted C1-C6 alkyl,
reacting the compound of formula (III) with a metal hydroxide or other suitable base to provide a compound of formula (I) or a salt thereof.