2-Bromoacetamide → (R)-2-(4-(2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-2-methylpiperazin-1-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

MeCN (2 mL) was added to 4-chloro-2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine, prepared as described in Example 16, (110 mg, 0.278 mmol) in a microwave vial. The vial was then charged with diisopropylethylamine (0.24 mL, 1.38 mmol) and (R)-2-methylpiperazine (56 mg, 0.556 mmol). The vial was sealed and heated via microwave irradiation at 100° C. for 45 minutes. The mixture was cooled to room temperature and then charged with 2-bromoacetamide (115 mg, 0.833 mmol), re-sealed and heated via microwave irradiation at 100° C. for 10 minutes. The reaction was then cooled to room temperature and adsorbed in vacuo onto silica and loaded onto a silica gel flash chromatography column for purification [0-10% (10% NH4OH)MeOH/DCM]. The material was then further purified by additional silica gel flash chromatography {0-35% [10% MeOH (containing 1% NH4OH)/EtOAc]/DCM} to furnish (R)-2-(4-(2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-2-methylpiperazin-1-yl)acetamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.27 (br. s., 1 H) 7.17 (d, J=7.58 Hz, 1 H) 7.13 (br. s., 1 H) 7.08 (d, J=7.58 Hz, 2 H) 5.72 (s, 1 H) 3.98 (s, 2 H) 3.59 (s, 3 H) 3.51-3.58 (m, 2 H) 3.25-3.32 (m, 3 H) 3.16-3.24 (m, 1 H) 3.11 (d, J=16.17 Hz, 1 H) 2.94 (br. s., 3 H) 2.71-2.85 (m, 3 H) 2.56-2.65 (m, 1 H) 2.05 (s, 6 H) 1.11-1.19 (m, 6 H) 1.00 (d, J=6.06 Hz, 3 H); MS (ESI+) m/z 517.34 (M+H)+.

Provenance & Evidence