Diisopropylethylamine → 4-[3-(2-Chloro-pyrimidin-4-yl)-benzyl]-2-(S)-methyl-piperazine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Intermediate 125 Methanesulfonic acid 3-(2-chloro-pyrimidin-4-yl)-benzyl ester (0.70 g) and Intermediate 126 2-(S)-Methyl-piperazine-1-carboxylic acid tert-butyl ester (0.61 g) with diisopropylethylamine (0.70 mL) in ethylene glycol dimethyl ether (20 mL) was refluxed for 3 hours, cooled to room temperature, evaporated under reduced pressure and the residue was dissolved in dichloromethane, washed with water (3×), brine, dried over dried over Na2SO4, chromatographed on silica gel (dichloromethane:methanol=98:2) to give 0.60 g of oily product with yield 64%. LC-MS showed the product had the expected M+H+ of 403. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 8.6 (s, 1H) 8.0 (s, 1H) 7.9 (d, 1H) 7.6 (d, 1H) 7.5 (m, 2H) 4.2 (S, 1 h) 3.8 (d, 1H) 3.4 (m, 2H) 3.0 (m, 1H) 2.7 (d, 1H). 2.6 (d, 1H) 2.1 (m, 2H) 1.5 (s, 9H) 1.2 (d, 3H).

Provenance & Evidence