反应详情

温度

27.5 °C

To a stirred solution of (E)-β-methyl-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naphthyridine-3,4′-piperidin]-2(4H)-one (Compound 34) (200 mg, 0.35 mmol) in methanol (3 mL) was added 37% formaldehyde solution (0.086 mL, 1.07 mmol), followed by triethylamine (0.15 mL, 1.07 mmol) at 20-35° C. and the mixture was continued stirring at 20-35° C. for 30 minutes. Then NaBH4 (20 mg, 0.53 mmol) was added slowly portionwise at 0° C. and the reaction mixture was allowed to stir at 20-35° C. for 16 h. The reaction mixture was rotary evaporated under vacuum to get residue which was purified by preparative HPLC to get the desired compound as an off-white solid (25 mg, 15%); 1H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.34 (s, 1H), 8.15 (s, 1H), 7.71 (d, J=2.9 Hz, 1H), 7.61 (d, J=2.5 Hz, 1H), 7.45 (d, J=15.6 Hz, 1H), 7.30-7.14 (m, 1H), 5.68-5.64 (m, 1H), 4.26-4.22 (m, 1H), 4.06-4.02 (m, 1H), 3.80-3.72 (m, 3H), 3.68-3.62 (m, 1H), 2.90 (s, 2H), 2.62-2.54 (m, 2H), 2.28-2.04 (m, 4H), 2.19 (s, 3H), 1.90-1.78 (m, 2H), 1.42-1.28 (m, 2H); LC-MS: 464.3 (M+1)+. Preparative HPLC conditions: Column-Phenomenex Luna C18 (2) (250×21.1 mm, 5μ), Mobile Phase: (A) 0.1% TFA(Aq); (B) ACN; Flow rate: 15 ml/min.

1. stirringto stir at 20-35° C. for 16 h
2. customThe reaction mixture was rotary evaporated under vacuum
3. customto get residue which
4. customwas purified by preparative HPLC