Sodium Carbonate → N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-(thiophen-2-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, 50 mg, 0.099 mmol), thiophene-2-boronic acid pinacol ester (25 mg, 0.119 mmol), PdCl2(dppf) (8 mg, 10.9 μmol) and saturated aqueous Na2CO3 (140 μl) in DME (420 μl) was sealed in a vial and purged with argon. The reaction mixture was stirred at 120° C. for 15 min in a microwave. The suspension was diluted with DCM and water, phases were separated and the aqueous layer was extracted with DCM (2×). 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 (2-4%) in DCM, followed by another purification eluting with a gradient of EtOAc (70-100%) in hexanes. Product fractions were combined, evaporated and dried to yield the title compound as a white solid. (UPLC-MS 3) tR 1.23 min; ESI-MS 509.2 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 8.31 (s, 1H), 7.62-7.55 (m, 2H), 7.44 (d, 1H), 7.31 (d, 1H), 7.18-7.13 (m, 1H), 5.57 (s, 1H), 5.33 (s, 1H), 4.10 (t, 2H), 3.66 (t, 2H), 3.48 (s, 11H), 2.91 (t, 2H), 2.09-2.00 (m, 2H).

Provenance & Evidence