Triethylamine → N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)methanesulfonamide

Participants

Reaction Steps

To a solution of N1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N2,N2-dimethylethane-1,2-diamine (intermediate 199, 780 mg, 2.53 mmol) and NEt3 (0.705 mL, 5.06 mmol) in DCM (20 ml) at 0° C. was added dropwise methanesulfonyl chloride (0.215 ml, 2.78 mmol) and the solution was allowed to stir for 2 h at room temperature. The reaction mixture was quenched by the addition of NaHCO3 and diluted. Phases were separated and the water phase was extracted with DCM (2×), organic phases were combined, dried using Na2SO4, filtered and concentrated. The crude product was purified by reversed phase preparative HPLC eluting with a gradient of MeCN and water (RP 6, H2O/MeCN 95:05 to 40:60 in 25 min). Fractions containing the product were collected, diluted with water and basified with NaHCO3. The mixture was concentrated and extracted with DCM, dried using Na2SO4, filtered and dried to yield the title compound as a colorless waxy solid. (UPLC-MS 3) tR 0.34 min, ESI-MS 387.2 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 7.26 (s, 1H), 6.56-6.52 (m, 1H), 5.01 (s, 1H), 4.33 (s, 2H), 3.32 (s, 6H), 3.28-3.23 (m, 2H), 3.11 (t, 2H), 3.06 (s, 3H), 2.66 (t, 2H), 2.24 (t, 2H), 2.08 (s, 6H), 1.80-1.73 (m, 2H).

Provenance & Evidence