Processes for the preparation of cis-4-[2-{[(3s,4r)-3-fluorooxan-4-yl]amino}-8-(2,4,6-trichloroanilino)-9h-purin-9-yl]-1-methylcyclohexane-1-carboxamide
AssigneeCelgene Corporation
InventorsZheng CHEN, Maryll Elaine GEHERTY, Matthew Michael KREILEIN, Xiaoling LU, Nanfei ZOU
Life of this patent
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Abstract
Provided herein are processes for the preparation of cis-4-[2-{[(3S,4R)-3-fluorooxan-4-yl]amino}-8-(2,4,6-trichloroanilino)-9H-purin-9-yl]-1-methylcyclohexane-1-carboxamide, alternatively named (1s,4s)-4-(2-(((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)amino)-8-((2,4,6-trichlorophenyl)amino)-9H-purin-9-yl)-1-methylcyclohexane-1-carboxamide, or a salt, solvate, hydrate, or isotopologue thereof.
Claims46
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, or isotopologue thereof, comprising
- (a) contacting Compound 1 of the formula:
- or a salt, solvate, hydrate, or isotopologue thereof, with Compound 2 of the Formula:
- or a salt, solvate, hydrate, or isotopologue thereof, to provide Compound 3 of the Formula:
- or a solvate, hydrate, or isotopologue thereof;
- (b) contacting Compound 3, or a solvate, hydrate, or isotopologue thereof, with Compound 4 of the Formula:
- or a solvate, hydrate, or isotopologue thereof, to provide Compound 5 of the Formula:
- or a solvate, hydrate, or isotopologue thereof;
- (c) reducing Compound 5, or a salt, solvate, hydrate, or isotopologue thereof with a reducing agent and a catalyst, to provide Compound 6 of the Formula:
- or a solvate, hydrate, or isotopologue thereof;
- (d) contacting Compound 6 or a salt, solvate, hydrate, or isotopologue thereof, with 2,4,6-trichlorophenyl isothiocyanate, to provide Compound 7 of the Formula:
- or a solvate, hydrate, or isotopologue thereof;
- (e) contacting Compound 7 or a solvate, hydrate, or isotopologue thereof with ethylcarbodiimide hydrochloride, to provide a compound of Formula (I), or a solvate, hydrate, or isotopologue thereof;
- and
- (f) optionally converting the compound of Formula (I), or a solvate, hydrate, or isotopologue thereof, to a citrate salt of the compound of Formula (I).
A process for preparing a compound of Formula (I):
- or a salt, solvate, hydrate, or isotopologue thereof, comprising
- (e) contacting Compound 7 of the Formula:
- or a solvate, hydrate, or isotopologue thereof with ethylcarbodiimide hydrochloride, to provide a compound of Formula (I), or a solvate, hydrate, or isotopologue thereof;
- and
- (f) optionally converting the compound of Formula (I), or a solvate, hydrate, or isotopologue thereof, to a citrate salt of the compound of Formula (I).
A process for preparing Compound 7:
- or a salt, solvate, hydrate, or isotopologue thereof, comprising
- (d) contacting Compound 6 of the Formula:
- or a solvate, hydrate, or isotopologue thereof, with 2,4,6-trichlorophenyl isothiocyanate.
A process for preparing Compound 6:
- or a salt, solvate, hydrate, or isotopologue thereof, comprising
- (c) reducing Compound 5 of the Formula:
- or a solvate, hydrate, or isotopologue thereof with a reducing agent and a catalyst.
A process for preparing Compound 5
- or a salt, solvate, hydrate, or isotopologue thereof, comprising
- (b) contacting Compound 3 of the Formula:
- or a solvate, hydrate, or isotopologue thereof, with Compound 4 of the Formula:
- or a solvate, hydrate, or isotopologue thereof.
A process for preparing Compound 3:
- or a salt, solvate, hydrate, or isotopologue thereof, comprising
- (a) contacting Compound 1 of the Formula:
- or a solvate, hydrate, or isotopologue thereof, with Compound 2 of the Formula:
- or a salt, solvate, hydrate, or isotopologue thereof.
Dependencies are inferred from the claim text.