Acetonitrile → (E)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide

Participants

Reaction Steps

To a suspension of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt (95 mg, 0.57 mmol) in acetonitrile (5 mL) was added 1 drop of DMF before introducing (COCl)2 (0.25 mL, 2.86 mmol). Resulting mixture was stirred at room temperature for 2 hours. Concentrated and dissolved in DCM (2 mL) before introduced to the solution of 6-amino-9-(3-(methylamino)phenyl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one (32) (100 mg, 0.24 mmol) in DCM (2 mL). Resulting solution was stirred at room temperature for 2 hours before quenched the reaction with MeOH (2 mL). Solvent was removed and the residue was pre-purified by column chromatography (silica gel, 0 to 10% methanol in methylene chloride (1% Et3N)) followed by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3)) to give (E)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide (33) (60 mg, 47%) as white solid. LC-MS (ESI): m/z (M+1) 536. 1H NMR (400 MHz, DMSO) δ 8.11 (s, 1H), 7.72-7.56 (m, 3H), 7.51-7.33 (m, 5H), 7.23-7.09 (m, 5H), 6.65 (dt, J=15.2, 6.1 Hz, 1H), 6.04 (d, J=16.6 Hz, 1H), 5.90 (br, 2H), 3.27 (s, 3H), 2.99 (s, 2H), 2.10 (s, 6H).

Provenance & Evidence