1,3-Dibromo-5,5-dimethylhydantoin → 4-[3-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-Phenyl]-piperazine-1-carboxylic acid tert-butyl ester

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Reaction Steps

The product from step 3 (160 mg. 0.40 mmol) was dissolved in 1 mL of DMF and 1 mL of THF was added. The mixture was cooled to −20° C. (isopropanol/ice/dry ice bath) and 1,3-dibromo-5,5-dimethyl hydantoin (58 mg, 0.20 mmol) was added in 4 portions over 40 minutes. The mixture was stirred for an additional 1 hour during which the internal temp rose to −5° C. It was diluted with a mixture of 1 mL of 2M Na2CO3, 1 mL of sat. Na2SO3 and 6 mL of water and the mixture stirred for 5 minutes. EtOAc (10 mL) was added and the layers were separated. The aqueous layer was extracted with 15 mL of EtOAc and the combined organic fractions were washed with 2M aqueous Na2CO3, water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by Isco®(Red-sep 12, eluting with 60-100% hexanes/EtOAc) to provide 157 mg (82%) of the title compound as a foamy solid. 1H-NMR (DMSO-d6) 7.98-7.64 (bs, 2H), 7.61 (s, 1H), 7.797 (s, 1H), 7.52 (d, 1H), 7.03 (d, 1H), 7.00-6.93 (m, 2H), (d, 1H), 6.71 (d, 1H), 3.43 (m, 4H), 3.13 (m, 4H), 1.40 (s, 9H); LC-MS [M+H]+=473, 475, RT=2.80 min.

Provenance & Evidence