反应详情

2,4-Dichloro-5-(trifluoromethyl)pyrimidine (0.546 g, 2.52 mmol) in 1:1 dichloroethane: tert-butanol was cooled to 0° C. under nitrogen. A 1.0 M solution of zinc(II) chloride in diethyl ether (3.43 mL, 3.34 mmol) was added, and the mixture stirred for one hour at 0° C. tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate (I93) (0.667 g, 2.29 mmol) in 1:1 dichloroethane:tert-butanol (20 mL) was added dropwise over thirty minutes, followed by triethylamine (0.351 mL, 2.52 mmol) in 1:1 dichloroethane:tert-butanol (10 mL). The mixture was stirred overnight, allowing the ice bath to come to room temperature over this time. The mixture was concentrated onto silica gel and chromatographed (40 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.) to give a residue which was triturated with petroleum benzine 40-60° C. to give the title compound (I94) (0.976 g, 90%) as an off white solid; 1H NMR (400 MHz, dr MeOD) δ 8.68 (d, J=0.6 Hz, 1H), 7.85 (d, J=8.6 Hz, 2H), 7.51 (d, J=8.6 Hz, 2H), 4.30 (s, 2H), 3.27-3.00 (br, overlaps with solvent), 1.47 (s, 9H). LCMS Method C, 5.08 min; m/z 472.1 [M+H]+; m/z 470.1 [M−H]−

1. customto come to room temperature over this time
2. concentrationThe mixture was concentrated onto silica gel
3. customchromatographed (40 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.)
4. customto give a residue which
5. customwas triturated with petroleum benzine 40-60° C.