Sodium hydride → HCID 68283104, compound

HRID 1469452Notes

Reaction equation

HRID 1469452 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[C:8]([CH3:13])=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[O:18]1[CH2:20][CH:19]1[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([CH2:20][CH:19]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[OH:18])[C:7]3[C:8]([CH3:13])=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5939582,6-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleHCID 109534834-(Oxiran-2-yl)pyridine

Product 1

HCID 68283104HCID 68283104, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,6-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 g, 5.00 mmol) in DMF (10 mL) was added sodium hydride (600 mg, 15 mmol) under nitrogen atmosphere at 0° C. and stirred for 10 min. 4-(Oxiran-2-yl)pyridine (1.08 g, 8.92 mmol) was added dropwise under nitrogen atmosphere. The reaction mixture was stirred at RT for 12 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was poured in ice-cold water and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (5×50 mL), dried over anhydrous sodium sulfate and concentrated. The residue was crystallized with diethyl ether to yield 2-(2,6-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.58 (d, 2H), 7.23 (m, 3H), 7.0 (t, 1H), 6.9 (d, 1H), 4.81 (t, 1H), 4.3-4.4 (m, 2H), 3.5 (dd, 2H), 3.0 (m, 1H), 2.8 (m, 1H), 2.75 (s, 3H), 2.7 (m, 1H), 2.6 (m, 1H), 2.43 (s, 3H). Separation by chiral HPLC provides enantiomers 82a and 82b.

Workup

  1. stirringThe reaction mixture was stirred at RT for 12 h
  2. customThe progress of reaction
  3. additionThe reaction mixture was poured in ice-cold water
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe combined organic layer was washed with water (5×50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was crystallized with diethyl ether

Sources & evidence

ORD record
ord-2cef7cadbc654234925428b4874db393
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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