Ethyl diazoacetate → ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-vinylpyrimidine (1-3) (1.00 g, 4.65 mmol, 1.0 eq.) in degassed toluene (20 mL) was added ethyl diazoacetate (0.98 mL, 9.30 mmol, 2.0 eq.) and the reaction was heated to 120° C. The reaction was monitored by LC-MS and after 2 h the mixture was cooled to room temperature and the toluene was removed by roto-evaporation. The resulting residue was purified by silica gel column chromatography (10-40% EtOAc/hexanes) to afford racemic ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate as a white solid. Further purification by chiral SFC provided the active isomer (1-4) as the second eluting peak that was used in subsequent reactions. Analytical separation conditions are as follows: Chiralcel OJ-H, 4.6 mm×25 cm, 90/10 CO2/MeOH+0.1% diethylamine, flow rate=2.4 mL/min; peak 1=2.0 min, peak 2=2.6 min. 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 4.17 (q, 2H, J=7.1 Hz), 2.88 (s, 3H), 2.64-2.55 (m, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.36 (ddd, 1H, J=8.6, 5.7, 3.8 Hz), 1.74-1.61 (m, 2H), 1.28 (t, 3H, J=7.1 Hz). MS: m/z=302 (M+H).

Provenance & Evidence