Aniline → HCID 44223338, compound

Participants

Reaction Steps

A round bottom flask equipped with a stir bar and nitrogen inlet was charged with aniline (4.2 mg, 0.046 mmol) and dry toluene (0.5 mL) under a nitrogen atmosphere. Trimethyl aluminum (8.0 μL, 0.160 mmol, 7 eq.) was added to this solution, and this mixture was stirred at room temperature for 20 minutes. Methyl 5-(2,6-difluoro-3-(propylsulfonamido)benzamido)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (13.5 mg, 0.023 mmol, see Example 14) was added in one portion, and the reaction mixture warmed to 90° C. for 30 minutes. The reaction mixture was then allowed to cool to room temperature. The mixture was then quenched carefully with 30% aqueous sodium potassium tartrate and extracted with ethyl acetate (2×). The extracts were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in THF (1 mL), and a 1M aqueous LiOH solution (1 mL) was then added. The mixture was stirred at room temperature for 16 hours, diluted with AcOH/water and extracted with EtOAc (2×). The extracts were washed with saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated. The resulting residue was subjected to preparative TLC purification (2×0.5 mm plates, 10% MeOH/DCM) to afford 5-(2,6-difluoro-3-(propylsulfonamido)benzamido)-N-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide (4.2 mg, 36%). 1H NMR (400 MHz, DMSO-d6) δ 12.31 (s, 1H), 10.97 (s, 1H), 9.76-9.87 (m 2H), 8.89-8.96 (m, 1H), 8.42-8.55 (m 2H), 7.73-7.80 (m, 2H), 7.51-7.59 (m, 1H), 7.20-7.38 (m, 3H), 7.03-7.11 (m, 1H), 3.06-3.14 (m, 2H), 1.71-1.82 (m, 2H), 0.94-1.04 (m, 3H); m/z (APCI-neg) M−1=512.1; (APCI-pos) M+1=514.0.

Provenance & Evidence