Sodium hydride → 11-(2-(pyridin-4-yl)-2-(hydroxy)ethyl)-7,8,9,9a,10,11-hexahydro-5H-pyrido[3',2':4,5]pyrrolo[3,2-f]indolizine

HRID 535878Notes

Reaction equation

HRID 535878 reaction equation
[CH2:1]1[CH:5]2[CH2:6][C:7]3[NH:8][C:9]4[C:14]([C:15]=3[CH2:16][N:4]2[CH2:3][CH2:2]1)=[CH:13][CH:12]=[CH:11][N:10]=4.[H-].[Na+].[O:19]1[CH2:21][CH:20]1[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>CN(C=O)C>[N:25]1[CH:26]=[CH:27][C:22]([CH:20]([OH:19])[CH2:21][N:8]2[C:7]3[CH2:6][CH:5]4[N:4]([CH2:3][CH2:2][CH2:1]4)[CH2:16][C:15]=3[C:14]3[CH:13]=[CH:12][CH:11]=[N:10][C:9]2=3)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 670365602,3,4,9,10,10a-hexahydro-1H-3a,8,9-triaza-cyclopenta[b]fluorene

Product 1

HCID 5135667211-(2-(pyridin-4-yl)-2-(hydroxy)ethyl)-7,8,9,9a,10,11-hexahydro-5H-pyrido[3',2':4,5]pyrrolo[3,2-f]indolizine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triaza-cyclopenta[b]fluorene (1 g, 4.6 mmol) in DMF (20 mL) were portion wise added NaH (60%, 0.552 g, 13.8 mmol) and 4-(oxiran-2-yl)pyridine (0.709 g, 5.6 mmol). The reaction mixture was stirred at RT overnight. The progress of reaction mass was monitored by LCMS. The reaction mixture was quenched with ice cold water (300 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with water (10×100 mL) followed by brine (2×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography followed by reverse phase HPLC to yield the title compound.

Workup

  1. customThe progress of reaction mass
  2. customThe reaction mixture was quenched with ice cold water (300 mL)
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. washThe combined organic layer was washed with water (10×100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-87156b69d83d4ea9b5ac21f1e00f7de1
Source dataset
uspto-grants-2014_10
Patent number
US08859561B2

Reaction notes

Loading…