Methanesulfonyl chloride → HCID 68515156, compound

Participants

Reaction Steps

To a stirred mixture of N-(4-(1-(4-methoxybenzyl)-3-(2-hydroxyethyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (100 mg, 0.16 mmol; prepared as in Example 8, Step C), DIEA (0.057 mL, 0.33 mmol), and chloroform (5 mL), cooled in an ice bath under N2 was added methanesulfonyl chloride (0.0189 mL, 0.244 mmol). The reaction was allowed to warm to room temperature slowly as the ice melted. The solution was stirred for 30 minutes at room temperature. A portion of the reaction mixture (1.25 mL) was transferred to a second flask and concentrated in vacuo. To the residue was added 1-methylpiperazine (0.023 mL, 0.20 mmol). The neat reaction mixture was heated to 100° C. for 1 hour. The crude was partitioned between DCM (2 mL) and a 1:1 saturated aqueous NaHCO3/water mixture (2 mL). The phases were separated, and the organic phase was dried (Na2SO4) and loaded directly on to a preparative TLC plate, eluting with 10% MeOH (containing 7N NH3) in CHCl3. Yield: 4 mg, 12%. 1H NMR (400 MHz, CDCl3) δ 10.02 (s, 1H), 8.36 (s, 1H), 8.28 (d, J=6 Hz, 1H), 7.76 (m, 1H), 7.47 (m, 2H), 7.30 (d, J=9 Hz, 2H), 7.26 (m, 1H, overlaps chloroform), 7.18 (t, J=9 Hz, 1H), 7.06 (t, J=9 Hz, 2H), 6.82 (d, J=9 Hz, 2H), 6.18 (d, J=6 Hz, 1H), 5.57 (s, 2H), 3.76 (s, 3H), 3.29 (m, 2H), 2.93 (m, 2H), 2.5-2.8 (m, 8H), 2.42 (s, 3H), 1.82 (m, 2H), 1.64 (m, 2H).

Provenance & Evidence