Methyl iodide → HCID 59239421, compound

Participants

Reaction Steps

To a solution of tert-butyl 2-chloro-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (dp) (501 mg, 1.41 mmol) in Tetrahydrofuran (14 mL) was added 1.7 M of tert-Butyllithium in Pentane (1.1 mL) at −78° C., which resulted orange color solution. The reaction was kept at −78° C. for 40 min before Methyl iodide (0.44 mL, 7.1 mmol) was injected. The solution was kept at −78° C. for another 40 min before quenching with water. The mixture was diluted by Dichloromethane, which was washed by water and brine till pH 7. After evaporation, the residue was purified on a silica gel column. Tert-butyl 2-chloro-8-methyl-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (qe) (452 mg, 87% yield) was obtained as white solid: 1H NMR (500 MHz, CDCl3) δ 5.02 (bs, 1H), 4.26 (bs, 1H), 3.91-3.79 (m, 2H), 3.79-3.67 (m, 2H), 3.61 (m, 2H), 3.36 (m, 2H), 2.89 (bs, 1H), 2.75 (bs, 1H), 2.46 (d, J=15.0 Hz, 1H), 1.50 (d, J=7.0 Hz, 3H), 1.48 (s, 9H); LC-MS m/z=369 (M+H). Tert-butyl 2-chloro-8,8-dimethyl-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (qf) (44 mg, 8% yield) was obtained as white solid: 1H NMR (400 MHz, CDCl3) δ 3.87-3.73 (m, 4H), 3.60-3.52 (m, 2H), 3.52-3.42 (m, 4H), 2.65-2.56 (m, 2H), 1.74 (s, 6H), 1.50 (s, 9H); LC-MS m/z=383 (M+H).

Provenance & Evidence