US 2010/0249207 A1 · SYNTHESIS OF PYRROLIDINE COMPOUNDS

Abstract

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.

Claims52

Dependent claims

A method for preparing a compound of formula (I) or a salt thereof:

wherein:
one of R1 and 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;
and
optionally 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;
and
wherein 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;
and
optionally 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.

29 more elements

A composition comprising

(1) a compound of formula (I) or a salt thereof
and/or
a compound of formula (III) or a salt thereof
wherein
one of R1 and 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;
and
optionally substituted C3-C10 cycloalkenyl;
W is C1-6 alkylene;
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;
and
wherein 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;
and
optionally substituted heterocycloalkyl including 5-10 atoms;
and
R7 is chosen from hydrogen and optionally substituted C1-C6 alkyl;
and
(2) a detectable amount of one or more compounds selected from:
N-((7R,8aS)-1,4-dioxooctahydropyrrolo[1,2-a]pyrazin-7-yl)benzamide or a salt thereof, i.e., a compound of formula
or a salt thereof;
triphenylphosphine;
triphenylphosphine oxide;
a hydrazine dicarboxylate;
triethylamine;
benzotriazole;
(2S,4R)-4-benzamido-1-(2-(tert-butylamino)acetyl)pyrrolidine-2-carboxylic acid or a salt thereof, i.e., a compound of formula:
or a salt thereof;
and a compound of formula (II) or a salt thereof:

38 more elements

Dependencies are inferred from the claim text.

Synthesis of pyrrolidine compounds

Life of this patent

Synthesis of pyrrolidine compounds

Life of this patent

Abstract

Claims52