Process for the preparation of arylethanolamine derivatives having an anti-obesity and anti-diabetic properties
AssigneeSmithKline Beecham Corporation
InventorsRonnie Maxwell Lawrence, Alan Millar
Life of this patent
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Abstract
The present invention is a process for the preparation of a compound of Formula (IA) or a pharmaceutically acceptable salt thereof: that includes preparing a diamide of Formula (II) or a pharmaceutically acceptable salt thereof:
Claims11
A process for preparation of a compound of Formula (IA) or a pharmaceutically acceptable salt thereof:
- wherein R1 is an aryl, pyridyl, thiazolyl, phenoxymethyl, or pyrimidyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6alkoxy, C1-6alkyl, hydroxymethyl, trifluoromethyl, —NR6R6, and —NHSO2R6, where each R6 is independently hydrogen or C1-4alkyl;
- R2 is hydrogen or C1-6alkyl;
- R3 is CO2R7 where R7 is hydrogen or C1-6alkyl;
- R4 and R5 are independently hydrogen, C1-6alkyl, or —CO2C1-6alkyl;
- and
- Y is N or OH
- comprising the step of preparing a diamide of Formula (II) or a pharmaceutically acceptable salt thereof:
- wherein R1 is an aryl, pyridyl, thiazolyl, phenoxymethyl, or pyrimidyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6alkoxy, C1-6alkyl, hydroxymethyl, trifluoromethyl, —NR6R6, and —NHSO2R6, where each R6 is independently hydrogen or C1-4alkyl;
- R2 is hydrogen or C1-6alkyl;
- R3 is CO2R7 where R7 is C1-6alkyl;
- R4 and R5 are independently hydrogen, C1-6alkyl, or —CO2C1-6alkyl;
- and
- Y is N or CH.
A process for the preparation of a compound of Formula (IA):
- wherein R1 is an aryl, pyridyl, thiazolyl, phenoxymethyl, or pyrimidyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6alkoxy, C1-6alkyl, hydroxymethyl, trifluoromethyl, —NR6R6, and —NHSO2R6, where each R6 is independently hydrogen or C1-4alkyl;
- R2 is hydrogen or C1-6alkyl;
- R3 is CO2R7 where R7 is hydrogen or C1-6alkyl;
- R4 and R5 are independently hydrogen, C1-6alkyl, or —CO2C1-6alkyl;
- and
- Y is N or CH, or a pharmaceutically acceptable salt thereof, comprising reduction of a compound of Formula (II):
- wherein R1 is an aryl, pyridyl, thiazolyl, phenoxymethyl, or pyrimidyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6alkoxy, C1-6alkyl, hydroxymethyl, trifluoromethyl, —NR6R6, and —NHSO2R6, where each R6 is independently hydrogen or C1-4alkyl;
- R2 is hydrogen or C1-6alkyl;
- R3 is CO2R7 where R7 is C1-6alkyl;
- R4 and R5 are independently hydrogen, C1-6alkyl, or —CO2C1-6alkyl;
- and
- Y is N or CH, or a pharmaceutically acceptable salt thereof, and optionally the step of hydrolysis of the resulting ester group R7 in Formula (IA) to produce a compound of Formula (IA) wherein R7 is H.
A compound of Formula (II) or a pharmaceutically acceptable salt thereof:
- wherein R1 is an aryl, pyridyl, thiazolyl, phenoxymethyl, or pyrimidyl group, optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6alkoxy, C1-6alkyl, hydroxymethyl, trifluoromethyl, —NR6R6, and —NHSO2R6, where each R6 is independently hydrogen or C1-4alkyl;
- R2 is hydrogen or C1-6alkyl;
- R3 is —CO2C1-6alkyl;
- R4 and R5 are independently hydrogen, C1-6alkyl, or —CO2C1-6alkyl;
- and
- Y is N or CH.
A process for the preparation of a compound of Formula (II) comprising reaction of a compound of Formula (III) with a compound of Formula (IV)
A compound of Formula (IV) or a pharmaceutically acceptable salt thereof:
- wherein:
- R2 is hydrogen or C1-6alkyl;
- R3 is —CO2C1-6alkyl;
- R4 and R5 are independently hydrogen, C1-6alkyl, or —CO2C1-6alkyl;
- and
- Y is N or CH.
Dependencies are inferred from the claim text.