Reaction Steps
To a suspension of 4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid (100 mg, 0.19 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate [TBTU] (68 mg, 0.21 mmol) in DMSO (1 mL) was added S-(−)-α-ethylbenzylamine (25 μL, 0.19 mmol) and N,N-diisopropylethylamine (67 μL, 0.38 mmol) dropwise at room temperature under N2. The mixture was stirred at room temperature for 1 hour under N2, and then poured into H2O (20 mL) under stirring. The resulting precipitate was extracted with AcOEt (20 mL). The organic layer was washed with H2O (3 times) and 10% NaHCO3, dried over MgSO4, and evaporated to give yellow amorphous. The oily residue was separated by silica gel column chromatography (AcOEt/n-hexane=10/1) to give pale yellow amorphous, which was solidified by the treatment of i-Pr2O. The resulting solid was collected by filtration, washed with i-Pr2O, and dried at 40° C. for 3 days under reduced pressure to give the title compound as pale yellow crystal (92 mg, 77%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.33 (d, J=7.0 Hz, 6H), 1.45 (d, J=7.3 Hz, 3H), 1.47 (s, 9H), 3.22 (septet, J=7.0 Hz, 1H), 5.16 (quintet, J=7.3 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 7.17-7.25 (m, 1H), 7.26-7.40 (m, 4H), 7.32 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.63 (d, J=8.5 Hz, 1H), 7.74 (br-d, J=8.4 Hz, 1H), 7.93 (br-s, 1H), 8.57 (s, 1H), 8.81 (d, J=7.3 Hz, 1H), 8.84 (d, J=8.5 Hz, 1H), 9.58 (s, 1H), 10.19 (s, 1H) MS ESI+ m/z: 635 (M+H)
