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

Participants

Reaction Steps

To a solution of (8-((5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate (intermediate 170, 368 mg, 0.657 mmol) in DCM (2.7 ml) at room temperature was added NEt3 (0.319 ml, 2.301 mmol) followed by 1-methylpiperazin-2-one (120 mg, 1.052 mmol). The reaction mixture was stirred at room temperature for 2 h and partitioned between DCM and water. The water layer was extracted multiple times with DCM, the combined organic layers were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography using a gradient of MeOH (0-3%) in DCM to yield the title compound as a white solid. (UPLC-MS 3) tR 0.87 min; ESI-MS 553.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 13.75 (s, 1H), 8.20 (s, 1H), 7.64 (br s, 1H), 7.58 (s, 1H), 5.56 (s, 1H), 5.23 (d, 1H), 4.06-4.01 (m, 2H), 3.70 (br s, 2H), 3.63 (t, 2H), 3.50-3.42 (m, 8H), 3.40 (s, 3H), 3.31 (br s, 2H), 3.14 (br s, 2H), 2.96 (br s, 3H), 2.87-2.80 (m, 2H), 2.71 (br s, 2H), 2.03-1.96 (m, 2H).

Provenance & Evidence