反应详情

To a solution of 1-[4-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamino)-phenyl]-piperazin-2-one (example 31, step 2) (180 mg, 0.47 mmol) in MeOH (4 mL) are added acetic acid (0.03 mL, 0.47 mmol), NaOAc (38 mg, 0.47 mmol) and acetone (0.2 mL, 1.18 mmol). The reaction mixture is stirred at room temperature for 1 hour then NaCNBH3 (60 mg, 0.94 mmol) is added and the mixture is stirred at 40° C. overnight. After cooling to room temperature, the reaction mixture is acidified with conc. HCl (pH 1) and concentrated in vacuo. The residue is partitioned between 6N NaOH and DCM. The aqueous layer is extracted with DCM (3×) and the combined organic layers are dried over MgSO4 and concentrated in vacuo to afford a crude compound which is purified by silica gel column chromatography. Elution with DCM and 98:2 DCM:MeOH affords the title compound as a yellow solid (45 mg, 25%).

1. stirringthe mixture is stirred at 40° C. overnight
2. temperatureAfter cooling to room temperature
3. concentrationconcentrated in vacuo
4. customThe residue is partitioned between 6N NaOH and DCM
5. extractionThe aqueous layer is extracted with DCM (3×)
6. dry with materialthe combined organic layers are dried over MgSO4
7. concentrationconcentrated in vacuo
8. customto afford a crude compound which
9. customis purified by silica gel column chromatography
10. washElution with DCM and 98:2 DCM