N-Trifluoroacetylprolyl chloride → (S)-1-(2,2,2-trifluoroethanoyl)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amide

関与物質

反応手順

A solution of 1-(5-amino-methoxyphenyl)-3-pyrazin-2-yl-urea (Compound 14, Example 4) (105 mg, 0.4 mmol) in dry pyridine (2 mL) at 0° C. was treated with a solution of N-trifluoroacetyl-(S)-prolyl chloride (0.1 M in dichloromethane, 4.5 mL, 0.45 mmol) and stirred 2 h at room temperature. The reaction was quenched with 1 N HCl (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with 1 N HCl (2×20 mL), water (20 mL), brine (20 mL), dried over sodium sulfate, and concentrated in vacuo to a beige solid (60 mg). Recrystallization from acetonitrile yielded the final solid product (30 mg, 17%). 1H NMR (300 Mhz, d6-DMSO) δ: (10.16-10.06, m, 3H), 8.90 (s, 1H), 8.36-8.30 (m, 2H), 8.25 (d, J=2.6 Hz, 1H), 7.42 (dd, J=8.8, 2.6 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 4.57 (dd, J=8.5, 4.4 Hz, 1 H), 3.88 (s, 3H), 3.73 (t, J=6.5 Hz, 1H), 2.27-2.21 (m, 1H), 2.06-1.90 (m, 3H). LRMS (ESI, positive) m/e 453.1 (M +1).

情報源と証拠