反应详情

(R)-tert-Butyl 3-hydroxypiperidine-1-carboxylate (Astatech Inc, Bristol, Pa.; 406 mg, 2.02 mmol) was added to a suspension of NaH (81 mg, 2.02 mmol) in THF (2.5 mL) and the resulting suspension was stirred at RT for 10 min. 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 75 mg, 0.25 mmol) was added and the resulting suspension was stirred at RT for 5 min, then heated at 70° C. for 5 h. The mixture was cooled to RT and partitioned between EtOAc (60 mL) and saturated aq. NH4Cl (20 mL). The organic layer was separated, sequentially washed with water (20 mL) tand brine (20 mL), then dried over MgSO4, filtered and concentrated in vacuo to give (R)-tert-butyl 3-((8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinolin-2-yl)oxy)piperidine-1-carboxylate as a light yellow solid. The material was used in the next step without further purification. m/z (ESI, +ve ion) 463.1 (M+H)+.

1. stirringthe resulting suspension was stirred at RT for 5 min
2. temperatureheated at 70° C. for 5 h
3. temperatureThe mixture was cooled to RT
4. custompartitioned between EtOAc (60 mL) and saturated aq. NH4Cl (20 mL)
5. customThe organic layer was separated
6. washsequentially washed with water (20 mL) tand brine (20 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo