Reaction Steps
Trifluoroacetic acid (0.109 mL, 1.43 mmol) and triethylsilane (44 μL, 0.28 mmol) were successively added at room temperature to a solution of crude ted-butyl 2-(1-(5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyrimidin-2-yl)pyrrolidin-3-yl)acetate B-8 (59.0 mg, 0.11 mmol) in anhydrous methylene chloride (0.25 mL) under an atmosphere of argon. The reaction mixture was stirred at room temperature for 12 h, then concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on C18 reverse phase (water:acetonitrile gradient with 0.05% formic acid) to give 2-(1-(5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyrimidin-2-yl)pyrrolidin-3-yl)acetic acid B-9 (22.3 mg, Yield=42% over 2 steps). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.01 (t, J=Hz, 3H), 1.63-1.74 (m, 3H), 2.12-2.18 (m, 1H), 2.42 (d, J=7.25 Hz, 2H), 2.52-2.64 (m, 1H), 3.15 (dd, J=7.88, 10.88 Hz, 1H), 3.46 (dd, J=7.88, 12.60 Hz, 1H), 3.48 (t, J=7.56 Hz, 1H), 3.63-3.69 (m, 1H), 3.80 (dd, J=7.41, 11.35 Hz, 1H), 4.03 (br d, J=13.08 Hz, 1H), 4.16 (q, J=6.69 Hz, 1H), 7.00 (t, J=7.41 Hz, 1H), 7.15 (br d, J=8.67 Hz, 1H), 7.18 (s, 1H), 7.29 (t, J=7.41 Hz, 2H), 7.50 (d, J=8.36 Hz, 2H), 7.51 (d, J=8.83 Hz, 1H), 8.66 (s, 2H), 9.14 (s, 1H), 12.22 (br s, 1H); MS (ESI) [M+1]+ 488.
