Sodium Carbonate → N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(2-methylthiazol-5-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-bromo-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 315, 300 mg, 0.594 mmol), 2-methylthiazole-5-boronic acid pinacol ester (250 mg, 1.066 mmol), PdCl2(dppf) (43.4 mg, 59 μmol) and saturated aqueous Na2CO3 (0.7 ml) in DME (2.5 ml) was sealed in a vial and purged with argon. The reaction mixture was stirred at 120° C. for 20 min in a microwave. Additional methylthiazole-5-boronic acid pinacol ester (20 mg, x mmol), the reaction mixture was purged with argon and was stirred at 120° C. for 10 min in a microwave. The suspension was diluted with DCM and saturated aqueous Na2CO3, phases were separated and the aqueous layer was extracted with DCM. The combined organic layers were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-10%) in DCM, followed by another purification eluting with a gradient of EtOAc (70-100%) in hexanes. Product containing fractions were combined, evaporated and dried to yield the title compound as a colorless solid. (UPLC-MS 3) tR 1.09 min; ESI-MS 524.1 [M+H]+.

Provenance & Evidence