Triethylamine → N-Methyl-N-(3-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-benzyl)-methanesulfonamide

Participants

Reaction Steps

(3-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol (63.0 mg, 0.152 mmol) was dissolved in N,N-dimethylformamide (3.00 mL) and triethylamine (27.5 μL, 0.198 mmol). Methanesulfonyl chloride (14.1 μL, 0.182 mmol) was added and the reaction was stirred at room temperature for 40 minutes. LCMS analysis showed complete conversion to the mesylate. In a clean round bottomed flask was added N-methyl-methanesulfonamide (332 mg, 3.04 mmol) in N,N-dimethylformamide (5.00 mL). Sodium hydride (29.2 mg, 1.22 mmol) was added and the reaction was stirred at room temperature for 5 minutes. The mesylate solution was then added and the reaction was stirred at room temperature for 2 hours. The reaction was partitioned between EtOAc (25 mL) and water (25 mL). The organic layer was washed twice with water (15 mL) and dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by prep-HPLC using a gradient of 10-55% AcN/water both containing 0.1% TFA as the eluting solvent. The product was then free based to obtain the title compound as a yellow solid (42 mg, 55%). m.p.=229-230° C.; LCMS (m/e) 506 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.69 (s, 1H), 8.15-8.08 (m, 2H), 7.56-7.46 (m, 3H), 7.38 (d, 1H, J=7.6 Hz), 7.00 (d, 1H, J=4.7 Hz), 6.93 (d, 2H, J=9.0 Hz), 6.82 (d, 1H, J=4.8 Hz), 6.68 (s, 1H), 4.40 (s, 2H), 3.22-3.15 (m, 4H), 2.86 (s, 3H), 2.79 (s, 3H), 2.63-2.56 (m, 4H), 2.37 (s, 3H).

Provenance & Evidence