Sulfoxonium, trimethyl-, iodide (1:1) → 2-(4-Chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[3-(oxetan-2-yl)propyl]amino}-2H-indazole-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

An oven-dried flask was charged with a mixture of potassium tert-butoxide (426 mg, 3.8 mmol) and trimethylsulfoxonium iodide (860 mg, 3.9 mmol) in anhydrous tert-butanol (7.5 mL) under argon. The reaction mixture was stirred vigorously at 50° C. for 5 h under argon then added to a stirred solution of crude (ii) (191 mg) in anhydrous tert-butanol (2.5 mL) in a single portion. The reaction was stirred at 50° C. overnight under argon, cooled to RT and concentrated in vacuo. The residue was then partitioned between water (50 mL) and EtOAc (50 mL) and the organics separated. The aqueous layer was extracted aq with EtOAc (2×50 mL) and the combined organic layers dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DMSO (2.5 mL) and the mixture centrifuged. The supernatant solution was collected and subjected to preparative HPLC (0.1% formic acid in acetonitrile: 0.1% formic acid in water, gradient elution 0% to 45% to 60% to 100%) to give Compound (4) (31 mg, 16% over 2 steps). 1H NMR (400 MHz, CD3CN) δ 7.80 (s, 1H), 7.60-7.50 (m, 4H), 7.35 (s, 1H), 6.98 (br s, 1H), 4.75-4.64 (m, 1H), 4.55-4.46 (m, 1H), 4.39-4.31 (m, 1H), 3.78-3.69 (m, 2H), 3.07 (s, 3H), 2.89 (d, J=4.8 Hz, 3H), 2.64-2.53 (m, 1H), 2.42-2.32 (m, 1H), 2.31-2.19 (m, 1H), 1.81-1.49 (m, 3H), 1.09-0.97 (m, 3H), 0.67-0.58 (m, 1H). ESI-MS m/z calculated for [M+H]+: 517.2. found: 517.0; m/z calculated for [M+Na]+: 539.2. found: 539.1.

Provenance & Evidence