Sodium hydride → HCID 89793619, compound

HRID 1055908Notes

Reaction equation

HRID 1055908 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[C:21]([C:28]3[NH:36][C:35]4[CH2:34][CH2:33][NH:32][C:31](=[O:37])[C:30]=4[CH:29]=3)[CH:22]=[CH:23][CH:24]=2)[N:19]=1>CN(C=O)C>[O:37]=[C:31]1[C:30]2[CH:29]=[C:28]([C:21]3[CH:22]=[CH:23][CH:24]=[C:25]4[C:20]=3[N:19]=[C:18]([O:1][CH:2]3[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]3)[CH:27]=[CH:26]4)[NH:36][C:35]=2[CH2:34][CH2:33][NH:32]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89793619HCID 89793619, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Similar to the method described in Example 103, tert-butyl 4-hydroxypiperidine-1-carboxylate (Aldrich; 357 mg, 1.77 mmol) was added to a suspension of NaH (70.9 mg, 1.77 mmol) in DMF (2.0 mL) and the resulting light yellow solution 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; 66 mg, 0.22 mmol) was added and the resulting dark red solution was stirred at RT for 5 min, then heated at 70° C. for 2.5 h. The mixture was cooled to RT and partitioned between EtOAc (100 mL) and saturated aq. NH4Cl (50 mL). The organic layer was separated, sequentially washed with water (40 mL) and brine (40 mL), and then dried over MgSO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH in DCM) gave tert-butyl 4-((8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinolin-2-yl)oxy)piperidine-1-carboxylate as an orange oil. m/z (ESI, +ve ion) 463.3 (M+H)+.

Workup

  1. stirringthe resulting dark red solution was stirred at RT for 5 min
  2. temperatureheated at 70° C. for 2.5 h
  3. temperatureThe mixture was cooled to RT
  4. custompartitioned between EtOAc (100 mL) and saturated aq. NH4Cl (50 mL)
  5. customThe organic layer was separated
  6. washsequentially washed with water (40 mL) and brine (40 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customChromatographic purification of the residue (silica gel, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-ff203ed4d6974896b6fd0c9811f38c19
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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