Methyl iodide → 1-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-8-(6-methoxymethyl-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Participants

Reaction Steps

To a mixture of 1-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-8-(6-hydroxymethyl-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 16.1, 28 mg, 0.068 mmol) in DMF (1 ml) was added NaH 55% (4 mg, 0.092 mmol) and the mixture was stirred for 20 min. Then iodomethane (0.006 ml, 0.096 mmol) was added and the RM was stirred again at rt for 30 min. After that, the RM was quenched with saturated aqueous NaHCO3 (20 ml) and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was dissolved in DMA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35). The fractions containing products were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting suspension was filtered and the cake was washed with water, before being dried under high vacuum to give the title compound as a white solid. (HPLC: tR 2.30 min (Method A); M+H=429 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.98 (s, 1H), 8.63 (s, 1H), 8.20 (s, 1H), 8.15-8.10 (m, 1H), 7.98-7.93 (m, 1H), 7.92-7.87 (m, 1H), 7.58-7.53 (m, 1H), 7.49-7.44 (m, 1H), 4.54-4.50 (m, 2H), 4.23-4.15 (m, 2H), 3.58 (s, 3H), 3.37 (s, 3H), 1.95 (s, 3H), 1.32 (t, 3H))

Provenance & Evidence