Sodium hydride → 1-(piperidin-1-yl)-2-(2,3,5,6-tetrahydro-1H-pyrido[3',2':4,5]pyrrolo[2,3-g]indolizin-7(11cH)-yl)ethanone

HRID 535871Notes

Reaction equation

HRID 535871 reaction equation
[CH2:1]1[CH:9]2[N:4]([CH2:5][CH2:6][C:7]3[NH:12][C:11]4[N:13]=[CH:14][CH:15]=[CH:16][C:10]=4[C:8]=32)[CH2:3][CH2:2]1.[H-].[Na+].Cl[CH2:20][C:21]([N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:22]>CN(C=O)C>[N:23]1([C:21](=[O:22])[CH2:20][N:12]2[C:7]3[CH2:6][CH2:5][N:4]4[CH:9]([C:8]=3[C:10]3[CH:16]=[CH:15][CH:14]=[N:13][C:11]2=3)[CH2:1][CH2:2][CH2:3]4)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2223122-Chloro-1-piperidine-1-yl-ethanoneHCID 670366062,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluorene

Product 1

HCID 513566731-(piperidin-1-yl)-2-(2,3,5,6-tetrahydro-1H-pyrido[3',2':4,5]pyrrolo[2,3-g]indolizin-7(11cH)-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 2,3,5,6,7,11c-hexahydro-1H-pyrido[3′,2′:4,5]pyrrolo[2,3-g]indolizine (120 mg, 0.565 mmol) in DMF (1 mL) was added a suspension of NaH (68.0 mg, 1.69 mmol) in DMF (1 mL). After stiffing for 5 min at RT, a solution of 2-chloro-1-(piperidin-1-yl)ethanone (272 mg, 1.69 mmol) in DMF (1 mL) was added dropwise into the reaction mixture and stirring continued for another 3 h. The progress of reaction was monitored by TLC and NMR. The reaction mixture was diluted with ice-water (20 mL) and extracted with EtOAc (3×25 mL). The organic layer was washed with water (3×20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by silica gel flash chromatography (10% MeOH-DCM) to yield 1-(piperidin-1-yl)-2-(2,3,5,6-tetrahydro-1H-pyrido[3′,2′:4,5]pyrrolo[2,3-g]indolizin-7(11cH)-yl)ethanone;

Workup

  1. waitcontinued for another 3 h
  2. customThe progress of reaction
  3. extractionextracted with EtOAc (3×25 mL)
  4. washThe organic layer was washed with water (3×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto afford crude material, which
  8. customwas purified by silica gel flash chromatography (10% MeOH-DCM)

Sources & evidence

ORD record
ord-3b5344fe9bc64cc1822749ce54665c07
Source dataset
uspto-grants-2014_10
Patent number
US08859561B2

Reaction notes

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