反应详情

温度

130 °C

A suspension of 140 mg of an isomeric mixture of methyl 5-(6-methoxy-3H-imidazo[4,5-c]pyridin-3-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate and methyl 5-(6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate (compounds B6a and B6b) in 20 ml of a saturated solution of ammonia in methanol was stirred in a microwave vial at 130° C. for 5 h in the microwave cavity. The reaction mixture was concentrated to dryness, the residue dissolved in 4 ml acetonitrile and 3 ml acidic buffer (KH2PO4, pH=2) and the isomers were separated and purified by preparative HPLC (acidic buffer/acetonitrile, 7/3 (v/v)). The acetonitrile was removed under vacuum and the aqueous solution was treated with NH4OH until pH 8-9 was reached. The aqueous solution was extracted with dichloromethane three times and the combined organic layers were dried and concentrated to dryness under vacuum to yield the title compound.

1. concentrationThe reaction mixture was concentrated to dryness
2. dissolutionthe residue dissolved in 4 ml acetonitrile
3. custom3 ml acidic buffer (KH2PO4, pH=2) and the isomers were separated
4. custompurified by preparative HPLC (acidic buffer/acetonitrile, 7/3 (v/v))
5. customThe acetonitrile was removed under vacuum
6. additionthe aqueous solution was treated with NH4OH until pH 8-9
7. extractionThe aqueous solution was extracted with dichloromethane three times
8. customthe combined organic layers were dried
9. concentrationconcentrated to dryness under vacuum