N-Methylbenzeneethanamine → (S)-5-(4-aminophenylthio)-4-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-N-(2-phenylpropyl)thiophene-2-carboxamide

Participants

Reaction Steps

The product of Example 90F (62 mg, 0.142 mmol) in dimethyl sulfoxide (2 mL) under a nitrogen atmosphere was reacted with (S)-(−)-□-methylphenethylamine (23 mg, 0.170 mmol), N,N-diisopropylethylamine (0.123 mL, 0.708 mmol), and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (55 mg, 0.170 mmol at room temperature for 20 hours. The reaction mixture was diluted with water (10 mL), and extracted with ethyl acetate (50 mL). The organic extract was washed sequentially with water (3×10 mL), saturated aqueous sodium hydrogencarbonate (20 mL), and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated by rotary evaporation. Purification of the residue by silica gel flash chromatography eluting with 4:96 methanol/methylene chloride afforded the title compound (67 mg, 0.121 mmol, 85%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.19 (d, J=6.99 Hz, 3 H) 1.33 (d, J=6.99 Hz, 6 H) 2.91-3.07 (m, 1 H) 3.14-3.29 (m, 1 H) 5.50 (s, 2 H) 6.51 (d, J=8.46 Hz, 2 H) 7.12 (d, J=8.82 Hz, 2 H) 7.16-7.34 (m, 5 H) 7.63 (d, J=8.46 Hz, 1 H) 7.77 (s, 1 H) 8.50 (t, J=5.88 Hz, 1 H) 8.62 (s, 1 H) 8.82 (d, J=8.82 Hz, 1 H) 9.97 (s, 1 H); MS (ESI+) m/z 555 (M+H)+, 1109 (2M+H)+, MS (ESI−) m/z 553 (M−H)−.

Provenance & Evidence