Piperidine → HCID 58529476, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (0° C.) solution of 4-{4-amino-5-[3-(benzyloxy)phenyl]pyrrolo[2,1-f][1,2,4]triazin-7-yl}butan-1-ol (80 mg, 0.21 mmol) in dichloromethane (1 mL) was added triethylamine (32 μL, 0.23 mmol) and methanesulfonyl chloride (17 μL, 0.22 mmol). The reaction was stirred (0° C.) for 4 h and then warmed to rt. The mixture was quenched with the addition of ice water (1 mL). The layers were separated and the organic layer was dried (Na2SO4) and evaporated. The residue was dissolved in DMF (1 mL) and potassium carbonate (85 mg, 0.62 mmol) and piperidine (18 μL, 0.22 mol) were added to the mixture. The reaction was stirred (60° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (15 mL) and water (15 mL). The layers were separated and the aqueous was further extracted with ethyl acetate (2×10 mL). The combined organics were dried (Na2SO4) and evaporated. The residue was purified by preparative HPLC using a gradient elution from 15% to 45% acetonitrile in water to obtain 4 mg (5%) of the desired product. 1H NMR (300 MHz, CD3CN) δ 7.86 (s, 1 H), 7.51-7.46 (m, 2 H), 7.45-7.32 (m, 4 H), 7.12-7.09 (m, 1 H), 7.09-7.06 (m, 1 H), 7.04-7.00 (s, 1 H), 6.56 (s, 1 H), 5.17 (s, 2 H), 2.96 (t, 2 H), 2.47-2.27 (m, 6 H), 1.83-1.73 (m, 2 H), 1.63-1.1.51 (m, 6 H), 1.48-1.40 (m, 2 H); ES-MS m/z 456.3 [M+H]+, HPLC RT (min) 2.29.

Provenance & Evidence