5-(2-Amino-ethyl)-2-(4-chloro-3-trifluoromethyl-phenoxy)-benzonitrile → HCID 178432725, compound

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Reaction Steps

5-(2-Methyl-pyrimidin-5-ylmethyl)-2-methylsulfanyl-1H-pyrimidin-4-one (50 mg, 0.201 mmol, 1 eq) and 5-(2-Amino-ethyl)-2-(4-chloro-3-trifluoromethyl-phenoxy)-benzonitrile (110 mg, 1.6 eq) were heated in a sealed vial at 130° C. for 20 hours. Solvent was then evaporated and the resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 10 g normal phase silica SNAP column and DCM/20% MeOH in DCM solvent system (gradient 5-50% of 20% MeOH in DCM in 25 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and the resulting oil was triturated with cyclohexane and diethyl ether to obtain 2-(4-chloro-3-trifluoromethyl-phenoxy)-5-{2-[5-(2-methyl-pyrimidin-5-ylmethyl)-4-oxo-1,4-dihydro-pyrimidin-2-ylamino]-ethyl}-benzonitrile (36 mg, yield=29.7%, purity=90%) in form of tain coloured powder. MS: [M+H]+=541.34. 1H NMR (300 MHz; CDCl3) δ/ppm 2.65 (s, 3H), 2.94 (t, J=7.02 Hz, 2H), 3.57 (s, 2H), 3.59-3.68 (m, 2H), 5.49 (br.s., 1H), 6.89 (d, J=8.61 Hz, 1H), 7.15 (dd, J=8.30 Hz, J=2.98 Hz, 1H), 7.38 (d, J=2.76 Hz, 1H), 7.44 (dd, J=8.82 Hz, J=1.91 Hz, 1H), 7.51 (d, J=8.51 Hz, 1H), 7.60 (d, J=2.02 Hz, 1H), 7.71 (s, 1H), 8.53 (s, 2H).

Provenance & Evidence