反应详情

A solution of 4-(4-fluorobenzyl)-3-oxopiperazine-1-carbonitrile (0.56 g, 2.40 mmol) and benzylamine (0.53 mL, 4.80 mmol) in 1,1,1,3,3,3-hexafluoroisopropanol (10 mL) was heated to reflux overnight. The solvent was removed in vacuo and the residue was purified by prep HPLC on a C18 column eluting with a water/acetonitrile/TFA gradient. The pure fractions were concentrated to an oil. The oil was partitioned between aqueous sat. NH4Cl and chloroform. The layers were separated and the aqueous layer was extracted twice more with chloroform. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to give an oil for the title compound. 1H NMR (400 MHz, d6 DMSO) before work-up δ 8.29 (t, 1H, J=5.5 Hz), 7.81 (bs, 2H), 7.29-7.40 (m, 7H), 7.19 (t, 2H, J=8.8 Hz), 4.56 (s, 2H), 4.45 (d, 2H, J=5.7 Hz), 4.15 (s, 2H), 3.67 (m, 2H), and 3.39 (m, 2H). ES MS (M+1)=341.3.

1. temperatureto reflux overnight
2. customThe solvent was removed in vacuo
3. customthe residue was purified by prep HPLC on a C18 column
4. washeluting with a water/acetonitrile/TFA gradient
5. concentrationThe pure fractions were concentrated to an oil
6. customThe oil was partitioned between aqueous sat. NH4Cl and chloroform
7. customThe layers were separated
8. extractionthe aqueous layer was extracted twice more with chloroform
9. dry with materialThe combined organic extracts were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated