2,6-Lutidine → 6-Arylpyrido[2,3-d]pyrimidine deriv. 74

Participants

Reaction Steps

To a solution of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (42 mg) from Example 20 in DMF (1 mL) was added 60% sodium hydride suspension (5 mg), and the mixture was stirred at room temperature for 0.5 hour. To the reaction mixture was added N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea (37 mg), and the mixture was stirred for 18 hours. The reaction mixture was diluted with dichloromethane (50 mL) and washed with water (2×15 mL). The organic layer was dried with sodium sulfate and concentrated. The resulting oil was purified on silica gel, eluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3) to afford a mixture of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (40 mg) and [[[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]imino[[1,1-dimethylethoxy) carbonyl]amino]methyl]ethylamino]carbamic acid-1,1-dimethylethyl ester. This mixture was dissolved in anhydrous dichloromethane (0.5 mL) containing 2.6-lutidine (8 mg). Trimethylsilyl trifluoromethanesulfonate (6 mg) was added, and the mixture was stirred at room temperature for 30 hours. The mixture was poured into saturated aqueous sodium bicarbonate, extracted with dichloromethane, dried over sodium sulfate, and concentrated. The resulting oil was chromatographed on silica gel, eluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3) to afford the title compound (7 mg), ESMS (1/4 MeOH/CH3CN+0.1% AcOH): m/z (relative intensity) 490.5 (MH+, 100), 491.5 (MH+ +1, 27), 492.5 (MH+ +2, 64).

Provenance & Evidence