Hydrochloric Acid → HCID 57761194, compound

Participants

Reaction Steps

To a solution of 4-{4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-piperidine-1-carboxylic acid tert-butyl ester (97 mg, 0.157 mmol) in dioxane, add 0.5 mL of HCl in dioxane (4M) and stir at room temperature for 2 hours. Concentrate the solution under reduced pressure and wash the residue with dry ether. Discard the ether wash, add additional ether and stir for one hour to give a pale yellow suspension. Collect the solid to afford 4-(3-chloro-4-fluoro-phenyl)-2-piperidin-4-yl-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine as the HCl salt. Prepare the freebase by partitioning between EtOAc and 10% NaOH solution. Dry (Na2SO4) and evaporate the EtOAc layer. Dissolve the free base in dichloroethane and add propionaldehyde (0.09 mmol) and sodium triacetoxyborohydride (22 mg, 010 mmol) followed by one drop of HOAc. Stir the mixture for one hour, dilute with DCM and wash with 10% NaOH (1×). Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Chromatograph the residue on a 2 mm preparative TLC plate (5% MeOH(1 N NH3)/DCM eluent) to give 4-(3-chloro-4-fluoro-phenyl)-2-(1-propyl-piperidin-4-yl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine. 1H NMR (CDCl3): δ 0.93 (t, 3H), 1.59 (m, 2H), 2.05 (m, 6H), 2.37 (m, 2H), 2.75 (m, 1H), 3.08)m, 2H), 3.40 (m, 4H), 3.88 (m, 4H), 6.69 (s, 1H), 7.06 (m, 1H), 7.21 (t, 1H), 7.86-7.93 (m, 2H), 8.08 (d, 1H), 8.47 (m, 1H).

Provenance & Evidence