Chlorosulfonic acid → HCID 178527433, compound

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A solution of 2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-ol Compound I-160 (56 mg, 1 equiv) and sulfurochloridic acid (552 μl) in a sealed vial was heated to 100° C. for 30 min. The mixture was diluted in ethyl acetate (50 ml) and washed with water (50 ml). The organic layer was dried, filtered and evaporated to give 79 mg of crude 2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)-4-hydroxypyrimidine-5-sulfonyl chloride as a white solid. The solid was combined with morpholine (47.4 μl, 3.3 equiv) and stirred at 25° C. for 30 min. The mixture was diluted in ethyl acetate (100 ml) and washed with water (50 ml). The organic layer was dried, filtered and evaporated to give crude oil. Purification by column chromatography (0 to 10% methanol in dichloromethane) gave 40 mg of the desired product (45%) as a white solid. 1H NMR (400 MHz, DMSO-d6) 9.11 (d, 1H), 8.01 (bs, 1H), 7.74-7.67 (m, 1H), 7.66 (s, 1H), 7.51 (t, 1H), 7.35-7.30 (m, 1H) 7.22 (s, 1H), 6.33 (bs, 1H), 5.97 (s, 2H), 3.52-3.46 (m, 4H), 2.67-2.59 (m, 4H).

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