Sodium hydride → HCID 68283943, compound

HRID 1630612Notes

Reaction equation

HRID 1630612 reaction equation
[CH3:1][C:2]1[CH:14]=[CH:13][C:12]2[NH:11][C:10]3[CH2:9][CH2:8][N:7]4[CH2:15][CH2:16][CH2:17][CH:6]4[C:5]=3[C:4]=2[CH:3]=1.[H-].[Na+].[O:20]1[CH2:22][CH:21]1[C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1>CN(C=O)C>[CH3:1][C:2]1[CH:14]=[CH:13][C:12]2[N:11]([CH2:22][CH:21]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[OH:20])[C:10]3[CH2:9][CH2:8][N:7]4[CH2:15][CH2:16][CH2:17][CH:6]4[C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 133195613-(Oxiran-2-yl)pyridineHCID 6703672110-methyl-2,3,5,6,7,11c-hexahydro-1H-indolizino[7,8-b]indole

Product 1

HCID 68283943HCID 68283943, compoundYield 19.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

9-Methyl-2,3,4,5,6,10c-hexahydro-1H-3a,6-diaza-cyclopenta[c]fluorene (200 mg, 0.88 mmol) was dissolved in DMF (3 ml), sodium hydride (106 mg, 2.65 mmol) was added and the mixture was stirred at RT for 15 min. 3-Oxiranyl-pyridine (214 mg, 1.76 mmol) was added dropwise into the reaction mixture and the mixture was stirred at RT for 3 h. The reaction was monitored by TLC and LCMS. After consumption of starting material, the reaction mixture was quenched with ice cold water (20 mL) and extracted with EtOAc (3×30 mL). The combined organic layer was washed with water (2×60 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by reverse phase chromatography to obtain 60 mg of 2-(9-Methyl-1,2,3,4,5,10c-hexahydro-3a,6-diaza-cyclopenta[c]fluoren-6-yl)-1-pyridin-3-yl-ethanol as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.7 (d, 1H), 8.53 (s, 1H), 8.4 (d, 1H), 7.85 (t, 1H), 7.25 (s, 1H), 7.08 (t, 1H),6.9 (d, 1H), 5.28 (t, 1H), 5.03 (t, 1H), 4.42 (s, 2H), 3.76 (m, 1H), 3.6 (m, 2H), 3.4 (m, 1H), 3.2 (m, 2H),2.7 (m, 1H), 2.38 (s, 3H), 2.2 (m, 3H). Separation by chiral HPLC provides diastereomers II-131a-d.

Workup

  1. stirringthe mixture was stirred at RT for 3 h
  2. customAfter consumption of starting material
  3. customthe reaction mixture was quenched with ice cold water (20 mL)
  4. extractionextracted with EtOAc (3×30 mL)
  5. washThe combined organic layer was washed with water (2×60 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto obtain the crude product, which
  9. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-a08214240cd3480f9de33be8d486106b
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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