Reaction Steps
Following a procedure analogous to that for the synthesis of Intermediate 12B of Example 12, 7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-2-naphthoic acid (Intermediate 46A 12 mg, 0.015 mmol) and morpholine (4 mg, 0.046 mmol) were converted to the title compound (3 mg, 20%). 1H NMR (1:1 CD3OD:CDCl3, 2:1 mixture of amide rotamers) δ 8.67 (s, 1H), 8.21 (d, J=8.3 Hz, 1H), 8.14 (dd, J=8.7, 1.5 Hz, 1H), 8.11 (d, J=1.7 Hz, 1H), 8.06 (s, 1H), 7.98 (t, J=7.6 Hz, 2H), 7.60 (d, J=8.3 Hz, 1H), 7.44-7.42 (m, 1H), 7.19-7.09 (m, 3.5H), 6.89 (d, J=7.2 Hz, 0.5H), 4.83 (br s, 1H), 4.50 (s, 1H), 4.36 (br s, 1H), 3.79 (br s, 4H), 3.68 (br s, 3H), 3.54 (br s, 3H), 3.45 (s, 1H), 3.00 (br s, 1.5H), 2.83 (br s, 1.5H), 2.29 (s, 2H), 2.24 (s, 1H), 1.50-1.44 (m, 1H), 1.40-1.35 (m, 2H), 1.32-1.16 (m, 4H), 1.12-0.99 (m, 2H), 0.92-0.86 (m, 3H), 0.75 (t, J=7.4 Hz, 2H), 0.68 (t, J=7.4 Hz, 1H); MS(ESI+) m/z 853.3 (M+H)+.
