Process for preparing an A2A-adenosine receptor agonist and its polymorphs
View Patent ↗Disclosed is a synthesis suitable for large scale manufacture of an A 2A -adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.
1. 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 optionally in the presence of acid.
2. The method of claim 1 , wherein the contacting is conducted in ethanol.
3. The method of claim 1 , wherein the acid is HCl up to 0.1 molar equivalent is used.
4. The method of claim 3 , wherein the contacting takes place at reflux.
5. The method of claim 1 , wherein about a 5-10 fold molar excess ethyl 2-formyl-3-oxoproionate is used.
6. The method of claim 5 , wherein about a 6.8-7.5 fold molar excess of ethyl 2-formyl-3-oxoproionate is used.
7. The method of claim 6 , wherein the compound of the formula (4) is isolated by
(a) cooling the completed reaction mixture to approximately 10° C.,
(b) filtering,
(c) washing the contents of the filter with ethanol, and
(d) drying the solid that remains under vacuum at a temperature that does not exceed 40° C.