反应详情

2,3,4-Trifluorobenzoic acid and 2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]aniline were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, followed by purification by chromatography on silica gel (50% EtOAc/PE as eluant), 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}benzoic acid was isolated as a cream-yellow solid (68%); m.p. (Et2O/hexane) 164-166° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.60 (v br s, 1 H), 9.27 (br s, 1 H), 7.83 (ddd, J=8.2, 6.1, 1.9 Hz, 1 H), 7.36 (dd, J=12.0, 1.7 Hz, 1 H), 7.21-7.11 (m, 2 H), 6.96 (td, J=8.8, 5.5 Hz, 1 H), 4.80 (br s, 1 H), 4.47 (d, J=16.0 Hz, 1 H), 4.38 (d, J=16.0 Hz, 1 H), 3.79-3.71 (m, 2 H), 3.51-3.45 (m, 2 H), 1.77-1.61 (m, 2 H), 1.56-1.44 (m, 4 H). Anal. calcd. for C21H18F3NO4: C, 62.2; H, 4.5; N, 3.5. Found C, 62.5; H, 4.4; N, 3.6. Step C: Preparation of 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide

1. customAfter workup, followed by purification by chromatography on silica gel (50% EtOAc/PE as eluant)