Potassium Carbonate → N-cyclopentyl-8-[2-(cyclopentylamino)-4-pyrimidinyl]-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine

Participants

Reaction Conditions

Reaction Steps

N-Cyclopentyl-8-iodo-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine (80 mg, 0.20 mmol) was dissolved in anhydrous toluene (5 mL). To this solution was added 2-(methylsulfanyl)-4-(tributylstannyl)pyrimidine (100 mg, 0.24 mmol,) and dichlorobis(triphenylphosphine)palladium (II] (14 mg, 0.1 equiv) and the resulting mixture heated at 100° C. for 24 hours. Ethyl acetate and water were added to the reaction mixture. The phases were separated and the organic phase washed with water, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (ethyl acetate:hexane 1:1) gave an inseparable mixture of the desired N-cyclopentyl-8-[2-(methylsulfanyl)-4-pyrimidinyl]-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine contaminated with N-cyclopentyl-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine. This mixture was dissolved in dichloromethane (15 mL) and 3-chloroperoxybenzoic acid (113 mg, 57–86%) was added. The resulting reaction mixture was stirred at room temperature for 1 hour. Dichloromethane and saturated aqueous potassium carbonate were added and the phases separated. The organic phase was washed with additional saturated aqueous potassium carbonate, water, dried over magnesium sulfate, filtered and concentrated to give a foam. This foam was dissolved in cyclopentylamine and the solution was heated at 60° C. for 3 hours. The mixture was concentrated in vacuo and the residue purified by silica gel chromatography (ethyl acetate:hexane 1:1) to give 20 mg (23% for 3 steps) of N-cyclopentyl-8-[2-(cyclopentylamino)-4-pyrimidinyl]-7-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine as a white foam. 1H-NMR (CDCl3): δ 8.39 (s, 1H), 8.28 (d, 1H), 7.67 (m, 2H), 7.46 (3H), 6.71 (d, 1H), 5.01 (d, 1H), 4.64 (m, 1H), 3.80 (m, 1H), 1.2–2.3 (m, 16H); MS m/z 441 (M+1).

Provenance & Evidence