Dichloromethane → N-((3,4-dichlorophenyl)(oxazol-5-yl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

Participants

Reaction Steps

A solution of (3,4-dichlorophenyl)(oxazol-5-yl)methanamine hydrochloride (22, 183 mg, 0.779 mmol), TEA (326 μL, 2.34 mmol) and DCM (5 mL) was stirred at RT for 10 min. CDI (158 mg, 0.974 mmol) was added and the reaction was stirred at RT for 1 h. A solution of 28 (211 mg, 0.779 mmol), TEA (326 μL, 2.34 mmol) and THF (2 mL) was stirred for 10 min then added to the solution and the resulting mixture stirred for 2 h at RT. The reaction was poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated. The crude product was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (2-5% MeOH/DCM). The recovered product was further purified by reverse phase column chromatography (SP4, 0-55% MeCN:water) to afford 82 mg (20.9%) of N-((3,4-dichlorophenyl)(oxazol-5-yl)methyl)-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide (30): 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.86 (s, 1H), 7.43 (m, 2H), 7.17 (dd, 1H). 6.93 (s, 1H), 6.30 (d, 1H), 5.09 (d, 1H), 4.88 (d, 1H), 4.37 (s, 2H), 4.05-3.95 (m, 3H), 3.68 (m, 2H), 3.54 (t, 2H), 2.70 (t, 2H), 2.01 (d, 2H), 1.59-1.46 (m, 2H); LCMS (ACPI-pos) m/z 505.5 (M+H)+.

Provenance & Evidence