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US 2020/0299228 A1Published application
Processes for the preparation of (s)-tert-butyl 4,5-diamino-5-oxopentanoate
AssigneeCelgene Corporation
InventorsJohn F. Traverse, Michael J. Zacuto, Weihong Zhang, Kirsten Faye Johnson, Maryll E. Geherty, Christopher Marton
Life of this patent
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Abstract
Provided are processes for the preparation of (S)-tert-butyl 4,5-diamino-5-oxopentanoate, or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof. Also provided are solid forms of various intermediates and products obtained from the processes.
Claims132
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, comprising
- (a) contacting a compound of Formula (II):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R1 is a suitable amino protecting group, with
- NH2—R2
- wherein R2 is hydrogen or a suitable amino protecting group, to provide a compound of Formula (III):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- (b) transforming the compound of Formula (III), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to a compound of Formula (IV):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- (c) deprotecting the —NH—R1 group and, when R2 is a suitable amino protecting group, deprotecting the —NH—R2 group to provide a compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- and
- (d) optionally converting the compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to a salt of the compound.
8 more elements
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, comprising
- (c) deprotecting the —NH—R1 group and, when R2 is a suitable amino protecting group, deprotecting the —NH—R2 group in a compound of Formula (IV):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R1 is a suitable amino protecting group, and R2 is hydrogen or a suitable amino protecting group, to provide a compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- and
- (d) optionally converting the compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to a salt of the compound.
2 more elements
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, comprising
- (a) contacting a compound of Formula (V):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R3 is a C1-10 alkyl, with NH3 to provide a compound of Formula (VI):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- (b) when R3 is not tert-butyl, transforming the R3 group to tert-butyl to provide a compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, and
- (c) optionally converting the compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to a salt of the compound.
3 more elements
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, comprising
- (a) contacting a compound of Formula (VIII):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R4 is a suitable amino protecting group, with a tert-butoxide nucleophile to provide a compound of Formula (IX):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- (b) deprotecting the —NH—R4 group to provide a compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- and
- (c) optionally converting the compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to a salt of the compound.
4 more elements
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, comprising
- (b) deprotecting the —NH—R4 group in a compound of Formula (IX):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R4 is a suitable amino protecting group, to provide a compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- and
- (c) optionally converting the compound of Formula (I), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to a salt of the compound.
2 more elements
A process for preparing a compound of Formula (I-rac):
- or a salt, solvate, hydrate, enantiomer, or isotopologue thereof, comprising
- (a) contacting a compound of Formula (XI):
- or a solvate, hydrate, or isotopologue thereof, wherein R5 is —CONH2, —CN, or —CO2R6, and R6 is a C1-10 alkyl, with tert-butyl acrylate in the presence of a base to provide a compound of Formula (XII):
- or a solvate, hydrate, or isotopologue thereof;
- (b) transforming the compound of Formula (XII), or a solvate, hydrate, or isotopologue thereof, to a compound of Formula (XIII):
- or a solvate, hydrate, or isotopologue thereof, in the presence of an acid;
- (c) when R5 is not —CONH2, transforming the R5 group to —CONH2 to provide a compound of Formula (I-rac), or a solvate, hydrate, or isotopologue thereof, wherein the —NH2 group in the compound of Formula (XIII), or a solvate, hydrate, or isotopologue thereof, is optionally protected and deprotected in step (c);
- (d) optionally separating the compound of Formula (I-rac), or a solvate, hydrate, or isotopologue thereof, to provide a compound of Formula (I):
- or a solvate, hydrate, or isotopologue thereof, via a chiral separation condition;
- and
- (e) optionally converting the compound of Formula (I), or a solvate, hydrate, or isotopologue thereof, to a salt of the compound.
8 more elements
A process for preparing a compound of Formula (I-rac):
- or a salt, solvate, hydrate, enantiomer, or isotopologue thereof, comprising
- (b) transforming a compound of Formula (XII):
- or a solvate, hydrate, or isotopologue thereof, wherein R5 is —CONH2, —CN, or —CO2R6, and R6 is a C1-10 alkyl, to a compound of Formula (XIII):
- or a solvate, hydrate, or isotopologue thereof, in the presence of an acid;
- (c) when R5 is not —CONH2, transforming the R5 group to —CONH2 to provide a compound of Formula (I-rac), or a solvate, hydrate, or isotopologue thereof, wherein the —NH2 group in the compound of Formula (XIII), or a solvate, hydrate, or isotopologue thereof, is optionally protected and deprotected in step (c);
- (d) optionally separating the compound of Formula (I-rac), or a solvate, hydrate, or isotopologue thereof, to provide a compound of Formula (I):
- or a solvate, hydrate, or isotopologue thereof, via a chiral separation condition;
- and
- (e) optionally converting the compound of Formula (I), or a solvate, hydrate, or isotopologue thereof, to a salt of the compound.
6 more elements
A process for preparing a compound of Formula (I-rac):
- or a salt, solvate, hydrate, enantiomer, or isotopologue thereof, comprising
- (a) contacting Compound 31 of the Formula:
- or a solvate, hydrate, or isotopologue thereof, with tert-butyl acrylate in the presence of a base to provide Compound 32 of the Formula:
- or a solvate, hydrate, or isotopologue thereof;
- (b) contacting Compound 32, or a solvate, hydrate, or isotopologue thereof, with NH3 to provide Compound 33 of the Formula:
- or a solvate, hydrate, or isotopologue thereof;
- (c) deprotecting the —NHBz group to provide a compound of Formula (I-rac), or a solvate, hydrate, or isotopologue thereof;
- (d) optionally separating the compound of Formula (I-rac), or a solvate, hydrate, or isotopologue thereof, to provide a compound of Formula (I):
- or a solvate, hydrate, or isotopologue thereof, via a chiral separation condition;
- and
- (e) optionally converting the compound of Formula (I), or a solvate, hydrate, or isotopologue thereof, to a salt of the compound.
8 more elements
A process for preparing a compound of Formula (XIV):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R7 is hydrogen or a suitable hydroxyl protecting group, comprising
- (a) contacting a compound of Formula (XV):
- or an analog of a compound of Formula (XV) that contains an aldehyde-equivalent and/or carboxylic-equivalent group, or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R8 is hydrogen, alkyl, or aryl, with a compound of Formula (I):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to provide a compound of Formula (XIV), or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- and
- (b) optionally crystallizing the compound of Formula (XIV), or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, from a solvent or mixture of solvents.
3 more elements
A process for preparing a compound of Formula (XV):
- or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R7 is hydrogen or a suitable hydroxyl protecting group, and R8 is hydrogen, alkyl, or aryl, comprising
- (a) contacting a compound of Formula (XVI):
- or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, with a formylating reagent, to provide a compound of Formula (XV), or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof;
- and
- (b) optionally crystallizing the compound of Formula (XV), or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, from a solvent or mixture of solvents.
2 more elements
A solid form comprising Compound 7 of the formula:
- wherein the solid form is Form A of Compound 7.
A solid form comprising racemic Compound 7 of the formula:
- wherein the solid form is Form A of racemic Compound 7.
A solid form comprising Compound 8 of the formula:
- wherein the solid form is Form A of Compound 8.
A solid form comprising racemic Compound 8 of the formula:
- wherein the solid form is Form A of racemic Compound 8.
A solid form comprising Compound 1 of the formula:
- wherein the solid form is Form A of Compound 1.
A solid form comprising Compound 1 of the formula:
- wherein the solid form is Form B of Compound 1.
A solid form comprising racemic Compound 1 of the formula:
- wherein the solid form is Form A of racemic Compound 1.
A solid form comprising Compound 35 of the formula:
- wherein the solid form is Form A of Compound 35.
A solid form comprising Compound 37 of the formula:
- wherein the solid form is Form 1 of Compound 37.
A solid form comprising racemic Compound 37 of the formula:
- wherein the solid form is Form 1 of racemic Compound 37.
A process for the preparation of O-t-Bu-DIC isourea of the structure:
- comprising reacting diisopropylcarbodiimide (DIC) with t-butanol and a Cu(I) salt in the presence of oxygen.
Dependencies are inferred from the claim text.