Ammonia → HCID 86622898, compound

Participants

Reaction Steps

4-[3-(2-Chloro-pyrimidin-4-yloxy)-phenoxymethyl]-benzonitrile (169 mg; 0.5 mmol; Example 6; Stage 6.1) is dissolved in CHCl3 (5 mL) and EtOH (0.5 mL) and cooled to 0° C. At this temperature, HCl gas is gently bubbled through during 20 min. The reaction mixture is kept at 4-5° C. for 72 h. After this time, pentane (10 mL) is added and stirring is continued for 1 h at 0° C. The supernatant is removed by decantation, and the residue (intermediate product) is suspended in MeOH (2 mL). At 0° C., NH3 (0.375 mL 2M solution in MeOH; 0.75 mmol) and NH4Cl (27 mg; 0.5 mmol) are added and the mixture is stirred at rt for 5 h 15 min. More NH3 (0.375 mL 2M solution in MeOH; 0.75 mmol) is added, as well as diethyl ether. After removal of the solvents under reduced pressure, the residue is taken up in EtOAc/water, extracted with water and brine and dried (Na2SO4). After filtration, the solvent is removed under reduced pressure to obtain a small amount of the title compound as free base. Since most of the product is in the aqueous layer, the latter is lyophilized and the residue purified twice over reversed phase silica (Lichroprep RP18; 15-25 μm), eluting with H2O/acetonitrile (0->43%) (0.1% TFA in both). After concentration of the solution, the title compound is isolated by lyophilization as TFA salt; ES-MS: [M+H]+; m/z=355; HPLC: AtRet=3.43 min.

Provenance & Evidence