Formaldehyde → N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

Participants

Reaction Conditions

Reaction Steps

A mixture of morpholine (35 mg, 41 mmol) and 100 uL acetic acid were sonicated until homogeneous, then treated with 37% aqueous formaldehyde (30 uL, 33 mg, 41 mmol) and the mixture added to a solution of N-[4-(4-amino-6-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea (150 mg, 34 mmol) in 1 mL acetic acid. This mixture was stirred for 16 h at 60° C. and then concentrated in vacuo. The residue was dissolved in methanol with 5 drops of trifluoroacetic acid and purified by RP-HPLC to provide the title compound as a white solid (32.3 mg, 17.1% yield). 1H-NMR (DMSO-d6) δ 9.34 (d, J=9.6 Hz, 1H), 8.94 (bs, 1H), 8.62 (d, J=7.2 Hz, 1H), 7.92 (s, 1H), 7.85 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.47 to 7.53 (m, m1H), 7.33 to 7.41 (m, 1H), 7.31 (d, J=8.7 Hz, 2H), 3.80 (s, 2H), 3.48 to 3.55 (m, 4H), 2.34 to 2.44 (m, 4H); MS [M+H]+=544.1; LCMS RT=2.70.

Provenance & Evidence