Sodium hydride → Dichloromethane methanol ammonium hydroxide

Participants

Reaction Steps

To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.6560 g, 2.513 mmol) in 10 mL of DMF was added sodium hydride, 60% dispersion in mineral oil (0.2010 g, 5.026 mmol) at 0° C. and the mixture was stirred at rt. After 10 min the mixture was added to a solution of 2-(chloromethyl)-3-(3-fluorophenyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochloride (0.8524 g, 2.513 mmol) in 5 mL of DMF and the resulting mixture was stirred at rt. After 3 h, the mixture was poured into ice-water (100 mL), the resulting precipitate was collected by filtration and washed with water (100 mL) to give a light yellow solid. The light yellow solid was purified by column chromatography on a 40 g Redi-Sep™ column using 0% to 100% gradient of DCM:MeOH:NH4OH (89:9:1) in DCM over 14 min and then 100% isocratic of DCM:MeOH:NH4OH (89:9:1) for 6 min as eluent to give the desired product as a light yellow solid. The light yellow solid was suspended in EtOAc and filtered to give 2-((4-amino-3-iodo-1H-pyrazolo-[3,4-d]pyrimidin-1-yl)methyl)-3-(3-fluorophenyl)-6-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.12 (1 H, s), 7.63 (1 H, dd, J=8.8, 6.8 Hz), 7.27-7.37 (1 H, m), 7.22 (1 H, dd, J=9.0, 0.8 Hz), 7.08-7.16 (2 H, m), 7.00-7.07 (1 H, m), 6.92-6.98 (1 H, m), 5.34 (2 H, s), 2.90 (3 H, s); Mass Spectrum (ESI) m/e=527.8 (M+1).

Provenance & Evidence