1,3-Dibromo-5,5-dimethylhydantoin → 5-Bromo-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-methylpyrrolo[2,1-f][1,2,4]triazin-4-amine (350 mg, 2.36 mmol) in DMF (5 mL), was added 4-methylenemorpholin-4-ium chloride (Eur. J. Med. Chem. 1989, 24, 379-384) (750 mg, 2.84 mmol) at rt. The reaction was stirred for 17 hr, cooled to −78° C., and treated with 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione (337 mg, 1.18 mmol). The reaction was allowed to stir for 30 minutes while warming to rt. The mixture was partitioned between ethyl acetate (200 mL) and saturated aqueous Na2CO3 solution (150 mL). The layers were separated and the organic phase was washed with brine, dried (Na2SO4), and concentrated to dryness. Trituration with acetonitrile afforded 300 mg (39%) of the desired product. 1H-NMR (DMSO-d6) δ 7.83 (s, 1H), 3.76 (s, 2H), 3.50-3.47 (m, 4H), 2.36-2.32 (m, 4H), 2.15 (s, 3H); MS [M+H]+=325.9, 327.9; LCMS RT=1.10.

Provenance & Evidence