反应详情

To a solution of 3-benzyloxy-5-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylic acid (50 mg, 0.166 mmol) in DMF (2 mL) were added EDC (32 mg, 0.166 mmol), HOBT (27 mg, 0.199 mmol), and 4-fluoro-N-methylbenzylamine (23 mg, 0.166 mmol). The reaction was stirred at room temperature overnight and partitioned between EtOAc and brine. The aqueous layer was extracted several times with EtOAc, and the combined organic extracts were dried over Na2SO4 and concentrated in vacuo. Purification by reverse phase chromatography on a C-18 column using a gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions afforded the title product. 1H NMR (400 MHz, CDCl3) δ 7.44-7.42 (m, 1H), 7.38-7.29 (m, 4H), 7.16-7.12 (m, 1H), 6.98-6.92 (m, 3H), 5.30-5.24 (m, 4H), 4.39-4.34 (m, 2H), 3.80-3.73 (m, 2H), 3.19-3.17 (d, 3H), 2.89-2.86 (d, 3H); ES MS (M+1)=423.

1. custompartitioned between EtOAc and brine
2. extractionThe aqueous layer was extracted several times with EtOAc
3. dry with materialthe combined organic extracts were dried over Na2SO4
4. concentrationconcentrated in vacuo
5. customPurification by reverse phase chromatography on a C-18 column
6. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions