Sodium hydride → 3-chloro-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 1497972Notes

Reaction equation

HRID 1497972 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[N:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH:8]3[CH2:15][CH2:16][CH2:17][N:7]3[CH2:6][C:5]2=1.[H-].[Na+].[O:20]1[CH2:22][CH:21]1[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1>CN(C=O)C>[Cl:1][C:2]1[CH:14]=[N:13][C:12]2[N:11]([CH2:22][CH:21]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[OH:20])[C:10]3[CH2:9][CH:8]4[N:7]([CH2:17][CH2:16][CH2:15]4)[CH2:6][C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 670365976-chloro-2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triaza-cyclopenta[b]fluorene

Product 1

HCID 584598733-chloro-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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-chloro-2,3,4,9,10,10a-hexahydro-1H-3a,8,9-triaza-cyclopenta[b]fluorene (700 mg, 2.82 mmol) in DMF (10 mL) were added portionwise NaH (60%, 338 mg 8.46 mmol) and 4-oxiranyl-pyridine (511 mg, 3.38 mmol). The reaction mass was stirred at RT for 16 h. The progress of reaction was monitored by LCMS. The reaction mass was quenched with ice cold water (200 mL) and extracted with EtOAc (3×150 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 (0-15% DCM/MeOH) followed by reverse phase HPLC to yield the title compound;

Workup

  1. customThe progress of reaction
  2. customThe reaction mass was quenched with ice cold water (200 mL)
  3. extractionextracted with EtOAc (3×150 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 (0-15% DCM/MeOH)

Sources & evidence

ORD record
ord-f9eb29659ab444ebb13eae702fb04294
Source dataset
uspto-grants-2015_12
Patent number
US09199996B2

Reaction notes

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