Acetyl chloride → (+/-)-2-(3-Oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)cyclohexyl acetate

Participants

Reaction Steps

(±)-2-(trans-2-Hydroxycyclohexyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 508, 50 mg, 0.11 mmol) was dissolved in dichloromethane (2 ml) and treated sequentially with diisopropylethylamine (0.028 ml, 0.16 mmol, 1.4 equiv), dimethyl-4-aminopyridine (1.4 mg, 0.011 mmol, 0.1 equiv) and acetyl chloride (0.014 ml, 0.19 mmol, 1.7 equiv). After stirring for 20 minutes, additional acetyl chloride (0.014 ml, 0.19 mmol, 1.7 equiv) was added and the mixture was stirred for an additional 20 minutes. The mixture was poured into water (15 mL) and extracted with dichloromethane (2×15 mL). The organic extracts were washed once with hydrochloric acid (10 mL, 1 N aqueous) and sodium bicarbonate (10 mL, aqueous saturated), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 80:20; dichloromethane:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.38 (1H, dd, J=6.1, 3.4 Hz), 8.36 (1H, s), 7.90 (1H, d, J=2.4 Hz), 7.72-7.70 (3H, m), 7.46-7.42 (2H, m), 7.39-7.36 (1H, m), 7.29-7.26, (2H, m), 6.47 (1H, dd, J=2.2, 1.9 Hz), 5.47 (1H, d, J=16.7 Hz), 5.42 (1H, d, J=16.2 Hz), 5.32-5.26 (1H, m), 4.56-4.49 (1H, m), 216-2.19 (2H, m), 2.13-1.99 (2H, m), 1.87 (3H, s), 1.89-1.81 (2H, m), 1.54-1.47 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 482.2202 [(M+H)+; calculated for C28H28N5O3: 482.2187].

Provenance & Evidence