5-(2-Amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)benzonitrile → HCID 178432723, compound

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5-(2-Methyl-pyrimidin-5-ylmethyl)-2-methylsulfanyl-1H-pyrimidin-4-one (50 mg, 0.20 mmol, 1 eq) and 5-(2-Amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)-benzonitrile (80 mg, 0.26 mmol, 1.3 eq) were heated at 130° C. (sealed bottle) in 500 μl of absolute ethanol for 24 hours. Solvent was then evaporated and the resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 11 g normal phase silica KP—NH column and DCM/10% MEOH in DCM solvent system (gradient 10-80% of 10% MeOH in DCM in 20 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and the resulting oil was triturated with hexane to obtain 5-{2-[5-(2-methyl-pyrimidin-5-ylmethyl)-4-oxo-1,4-dihydro-pyrimidin-2-ylamino]-ethyl}-2-(5-trifluoromethyl-pyridin-2-yloxy)-benzonitrile (36 mg, yield=32.4%, purity=92%) in form of tain coloured powder. MS: [M+H]+=508.40. 1H NMR (300 MHz; CDCl3) δ/ppm 2.64 (s, 3H), 2.94 (t, J=7.23 Hz, 2H), 3.53 (s, 2H), 3.57-3.66 (m, 2H), 7.14-7.23 (m, 2H), 7.51 (d, J=8.37 Hz, 2H), 7.55-7.64 (m, 2H), 7.96 (d, J=8.60 Hz, 1H), 8.34 (s, 1H), 8.50 (s, 2H).

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