Sodium Carbonate → N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(1,3-dimethyl-1H-pyrazol-4-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, 41 mg, 0.081 mmol), 1,5-dimethyl-1H-pyrazole-4-boronic acid pinacolester (19 mg, 0.083 mmol), PdCl2(dppf) (6 mg, 8.20 μmol) and saturated aqueous Na2CO3 (100 μl) in DME (300 μl) was sealed in a vial and purged with argon. Then reaction mixture was stirred at 120° C. for 15 min in a microwave. Additional 1,5-dimethyl-1H-pyrazole-4-boronic acid pinacolester (5 mg, 0.022 mmol) was added and the reaction mixture was stirred at 120° C. for 5 min in a microwave. The suspension was diluted with DCM and water, phases were separated and the aqueous layer was extracted with DCM. The combined organic layers were washed with water, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (1-5%) in DCM. Product fractions were combined, evaporated and dried to yield the title compound as an orange film. (UPLC-MS 3) tR 0.94 min; ESI-MS 521.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 8.24 (s, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 7.29 (s, 1H), 5.34 (s, 1H), 5.24 (s, 1H), 4.09-4.04 (m, 2H), 3.86 (s, 3H), 3.63 (t, 2H), 3.51-3.45 (m, 2H), 3.41 (s, 9H), 2.85 (t, 2H), 2.18 (s, 3H), 2.06-1.99 (m, 2H).

Provenance & Evidence