反应详情

To a solution of 1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone dihydrochloride (29.5 mg, 0.100 mmol, from Step B of Example 1.1), 3-methyl-1H-pyrazole-5-carboxylic acid (18.9 mg, 0.150 mmol), and triethylamine (0.139 mL, 1.00 mmol) in DMF (0.5 mL) was added 1-propylphosphonic acid anhydride solution (50 wt. % in ethyl acetate, 122 μL, 0.200 mmol). The mixture was stirred for 2 h, quenched with water and purified by preparative HPLC/MS. The resultant lyophilate was dissolved in DCM, treated with MP-carbonate resin (˜100 mg). The mixture was stirred for 30 min and filtered to remove the resin. The solvent was removed under reduce pressure to afford the title compound (26.0 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 2.34 (s, 3H), 2.66 (bs, 4H), 3.82 (s, 2H), 3.88 (bs, 2H), 4.02 (bs, 2H), 6.38 (s, 1H), 7.14 (t, J=8.59 Hz, 2H), 7.99-8.09 (m, 2H). Exact mass calculated for Cl17H19FN4O2: 330.2. Found: LCMS m/z=331.3 (M+H+).

1. customquenched with water
2. custompurified by preparative HPLC/MS
3. dissolutionThe resultant lyophilate was dissolved in DCM
4. additiontreated with MP-carbonate resin (˜100 mg)
5. stirringThe mixture was stirred for 30 min
6. filtrationfiltered
7. customto remove the resin
8. customThe solvent was removed