Example 22
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Step 1: 1-methyl-N-tetrahydropyran-3-yl-pyrazol-4-amine. General procedure A was followed using 1-methylpyrazol-4-amine and tetrahydropyran-3-one. The crude product was purified by prep-HPLC (column: Phenomenex Gemini C18 10 μm 250×50 mm; mobile phase: [water (10 mM NH4HCO3)-ACN]; B: 0-30%, 21 min) to give the title compound as a red oil. 1H NMR (400 MHz, chloroform-d) δ=7.12 (s, 1H), 6.93 (s, 1H), 3.92 (d, J=11 Hz, 1H), 3.81 (s, 3H), 3.77-3.68 (m, 1H), 3.59-3.48 (m, 1H), 3.38-3.30 (m, 1H), 3.12-3.01 (br. s, 1H), 2.04-1.92 (m, 1H), 1.80-1.68 (m, 1H), 1.67-1.48 (m, 2H).
Step 2:3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-1-[(1-methyl-1H-pyrazol-4-yl)(oxan-3-yl)sulfamoyl]urea sodium salt. General procedure B was followed using {[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]amino}sulfonyl chloride and 1-methyl-N-tetrahydropyran-3-yl-pyrazol-4-amine. The crude product was purified by prep-HPLC (column: Phenomenex Gemini C18 10 μm 250×50 mm; mobile phase: [water (10 mM NH4HCO3)-ACN]; B: 7-37%, 21 min) to give the title compound as a white solid. 1H NMR (400 MHz, MeOD) δ=7.68 (s, 1H), 7.40 (s, 1H), 6.98 (s, 1H), 4.26-4.13 (m, 1H), 4.12-4.06 m, 1H), 3.88 (s, 3H), 3.79-3.71 (m, 1H), 3.13-3.04 (m, 2H), 2.88 (t, J=8 Hz, 4H), 2.80 (t, J=7 Hz, 4H), 2.12-2.04 (m, 5H), 1.79-1.60 (m, 2H), 1.39-1.26 (m, 1H).
LC-MS (ESI): m/z: [M+H]+=460.1