Sodium hydride → (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

HRID 1055911Notes

Reaction equation

HRID 1055911 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[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>C1COCC1>[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][C@@H:2]3[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]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 1514398(R)-1-Boc-3-hydroxypiperidineHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89784696(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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(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)+.

Workup

  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

Sources & evidence

ORD record
ord-cfda1c5d575a4ca59168d4b025d7536e
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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