Process for preparing an A2A-adenosine receptor agonist and its polymorphs
AssigneeGilead Palo Alto, Inc.
InventorsJeff Zablocki, Elfatih Elzein
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Abstract
Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph. The A2A-adenosine receptor agonist has the following formula: This compound is prepared by reacting the ethyl ester with methylamine in a sealed pressure reactor.
Claims13
A method for the large scale preparation of (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide:
- comprising:
- reacting a compound of the formula (3)
- with methylamine wherein the compound of formula (3) is reacted with an aqueous solution of methylamine at an initial temperature of about 0-5° C. followed by warming to about 50-70° C. in a sealed pressure reactor.
A method of preparing a compound of the formula (3):
- comprising:
- reacting a compound of the formula (2)
- with ethyl 2-formyl-3-oxopropionate wherein about 1.1 molar equivalent of ethyl 2-formyl-3-oxopropionate is reacted with the compound of formula (2) in a solvent.
A method of synthesizing (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide
- comprising by contacting a compound of the formula (4):
- with an aqueous solution of methylamine at an initial temperature of about 0-5° C. followed by warming to about 50-70° C. in a sealed pressure reactor.
A method of synthesizing a compound of the formula (4):
- comprising
- contacting a compound of the formula (2):
- with an excess of ethyl 2-formyl-3-oxopropionate wherein about a 2-10 fold molar excess of ethyl 2-formyl-3-oxopropionate is reacted with the compound of the formula (2) in a solvent.
Dependencies are inferred from the claim text.