Oxalyl chloride → (E)-N-(3-(6-amino-7-(4-chlorophenyl)-8-oxo-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)but-2-enamide

Participants

Reaction Steps

To a suspension of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride salt (94 mg, 0.57 mmol) in dry acetonitrile (5 mL) was added 1 drop of DMF before introducing (COCl)2 (0.5 mL, 5.3 mmol). Resulting mixture was stirred at room temperature for 1 hour. Concentrated and dissolved in dry DCM (2 mL) before introducing a solution of 6-amino-9-(3-aminophenyl)-7-(4-chlorophenyl)-7H-purin-8(9H)-one (13) (100 mg, 0.28 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 (0.3% Et3N)) followed by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3.H2O)) to give (E)-N-(3-(6-amino-7-(4-chlorophenyl)-8-oxo-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)but-2-enamide (14) (25 mg, 19.1%) as a white solid. LC-MS (ESI): m/z (M/M+2) 464/466. 1H NMR (400 MHz, DMSO) δ 10.57 (s, 1H), 9.82 (s, 1H), 8.11 (s, 1H), 7.99 (s, 1H), 7.71 (d, J=8.5 Hz, 1H), 7.62 (d, J=8.7 Hz, 2H), 7.56-7.45 (m, 3H), 7.35 (d, J=8.8 Hz, 1H), 6.82-6.65 (m, 1H), 6.46 (d, J=15.3 Hz, 1H), 5.98 (s, 2H), 4.01-3.87 (m, 2H), 2.79 (s, 3H), 2.78 (s, 3H).

Provenance & Evidence