2-Chlorobenzoic Acid → 3-n-Butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]-3-fluorobiphenyl-4-yl]methyl]-1-[2-chloro-5-(propionylamino)phenyl]-1H-pyrazole-5-carbonitrile

関与物質

反応手順

By the procedure of Example 1, Step H, 2-chlorobenzoic acid was converted to its imidazolide and reacted with 3-n-butyl-1-[2-chloro-5-(propionylamino)phenyl]-4-[[3-fluoro-2'-sulfamoylbiphenyl-4-yl]methyl]-1H-pyrazole-5-carbonitrile (from Step K). The crude product was purified by semipreparative HPLC on a Zorbax C8 reverse phase column (elution with 75:25 acetonitrile-H2O containing 0.1% TFA), affording a 74% yield of the title compound as a cream-colored, stiff foam; homogeneous by TLC in 95:5 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 732 (M+1)+. 400 MHz 1H NMR (CDCl3) δ0.93 (t, J=7.3 Hz, 3H), 1.22 (t, J=7.5 Hz, 3H), 1.40 (m, 2H), 1.68 (m, 2H), 2.39 (q, J=7.5 Hz, 2H), 2.67 (t, J=7.8 Hz, 2H), 3.93 (br s, 2H), 7.1-7.7 (m, 12H), 7.77 (d, J=2.3 Hz, 1H), 8.37 (dd, J=7.9, 1.4 Hz, 1H), 9.10 (s, 1H).

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