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

Participants

Reaction Steps

To a mixture of 4-(dimethylamino)but-2-enoic acid hydrochloride (81 mg, 0.49 mmol) and 1 drop of DMF in 3 mL dry CH3CN was added 0.5 mL oxalyl chloride dropwise under N2. The reaction mixture was stirred at rt for 1 hr, then concentrated to dryness in vacuo. The resulting solid was dissolved in 2 mL dry DCM and was transferred to a stirred solution of 6-amino-9-(3-aminophenyl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one (7) (100 mg, 0.24 mmol) and one drop of TEA in 3 mL dry DCM in an ice-water bath. After stirring for 2 hrs, the reaction was quenched with MeOH. The resulting mixture was concentrated to dry, pre-purified by column chromatography (silica gel, 0 to 5% methanol in DCM), followed by Gilson using 10 to 95% acetonitrile in water (0.1% TFA) to give (E)-N-(3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl)-4-(dimethylamino)but-2-enamide (8) (61 mg, 48%) as a white solid. 1H NMR (400 MHz, DMSO) δ 10.56 (s, 1H), 9.79 (s, 1H), 8.11 (s, 1H), 8.00 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 7.58-7.32 (m, 6H), 7.25-7.07 (m, 5H), 6.84-6.65 (m, 1H), 6.46 (d, J=15.4 Hz, 1H), 5.88 (s, 2H), 4.02-3.87 (m, 2H), 2.79 (s, 3H), 2.78 (s, 3H). LC-MS (ESI): m/z (M+1) 522.

Provenance & Evidence