Tetrahydrofuran → HCID 66769738, compound

Participants

Reaction Steps

Synthesis of (E)-N-3-(6-[3-methylphenyl]aminopyrimidin-4-yl)aminophenyl-4-piperazinyl-2-butenamide (I-57) To a stirring solution at 0° C. under N2 of N-[3-(6-{3-methylphenyl}amino-pyrimidin-4-ylamino)-4-bromo-2-butenamide (Int-D) (2.15 g, 4.91 mmol) and triethylamine (0.86 mL, 6.17 mmol) in 10 mL of THF was added dropwise a solution of 1-Boc-piperazine (0.92 g, 4.91 mmol) in 10 mL of THF. The solution was allowed to warm to room temperature overnight, was concentrated and was then partitioned between EtOAc and sat. NaHCO3 solution. The organic extract was washed with brine solution, was dried (MgSO4), was filtered and was concentrated to give 2.76 g of 4-{3-[3-(6-{3-methylphenyl}amino-pyrimidin-4-ylamino)-phenylcarbamoyl]-allyl}-piperazine-1-carboxylic acid tert-butyl ester as gummy brown solid. This material was dissolved in 100 mL of CH2Cl2. 20 mL of trifluoroacetic acid was added and the mixture was stirred at room temperature under N2 for 2 h. The mixture was concentrated in vacuo, was basified with sat. NaHCO3 solution and was extracted with EtOAc (2×100 ml). The combined organic extract was dried (MgSO4), was filtered and was concentrated in vacuo. The residue was chromatographed (silica gel, 5% MeOH in CHCl3 [500 mL] then 1% NH4OH-10% MeOH in CHCl3) to give 0.404 g of (E)-N-3-(6-[3-methylphenyl]aminopyrimidin-4-yl)aminophenyl-4-piperazinyl-2-butenamide. (I-57) MS (m/z): 444 (M+1, 100%). 1H NMR (DMSO-d6) δ 10.03 (s, 1H), 9.17 (s, 1H), 9.07 (s, 1H), 8.27 (s, 1H), 7.90 (s, 1H), 7.17-7.36 (m, 6H), 6.79-6.80 (d, 1H), 6.72-6.75 (m, 1H), 6.29 (d, 1H), 6.20 (s, 1H), 3.08-3.39 (m, containing water and ˜3H), 2.70-2.72 (m, 4H), 2.30-2.42 (m, 4H), 2.29 (s, 3H.

Provenance & Evidence