Sodium hydride → 1-(3,4-Dimethoxy-phenyl)-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethanol

HRID 1469445Notes

Reaction equation

HRID 1469445 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH:28]2[CH2:30][O:29]2)[CH:23]=[CH:24][C:25]=1[O:26][CH3:27]>CN(C=O)C>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH:28]([OH:29])[CH2:30][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)[CH:23]=[CH:24][C:25]=1[O:26][CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 104197742-(3,4-Dimethoxyphenyl)oxirane

Product 1

HCID 601971751-(3,4-Dimethoxy-phenyl)-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethanolYield 25.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.2 g, 6.0 mmol) in 6 mL DMF, was added sodium hydride (720 mg, 12 mmol) under nitrogen at 0° C. and stirred for 5 min. 2-(3,4-Dimethoxy-phenyl)-oxirane (2.16 g, 18 mmol) was diluted in DMF (2 mL) and added dropwise to the reaction mixture under nitrogen atmosphere. The reaction mixture was stirred at RT for 5 h. After consumption of starting material (TLC and LCMS), the reaction mixture was poured in ice-cold water and extracted with EtOAc (3×50 mL). The combined organic layer was washed with water (5×30 mL) and dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (silica gel 100-200 mesh, eluent: 6% MeOH in DCM) to obtain 590 mg of 1-(3,4-dimethoxy-phenyl)-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 7.19 (m, 2H), 6.98 (d, 1H), 6.83 (m, 2H), 6.78 (s, 1H), 4.98 (t, 1H), 4.1 (m, 2H), 4.83 (s, 3H), 4.8 (s, 3H), 3.6 (dd, 2H), 2.68-2.88 (m, 3H), 2.53 (m, 1H), 2.5 (s, 3H), 2.4 (s, 3H). Separation by chiral HPLC provides enantiomers 66a and 66b.

Workup

  1. additionadded dropwise to the reaction mixture under nitrogen atmosphere
  2. stirringThe reaction mixture was stirred at RT for 5 h
  3. customAfter consumption of starting material (TLC and LCMS)
  4. additionthe reaction mixture was poured in ice-cold water
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined organic layer was washed with water (5×30 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. custompurified by column chromatography (silica gel 100-200 mesh, eluent: 6% MeOH in DCM)

Sources & evidence

ORD record
ord-68f86983b0d04a5795b58f141164ab8f
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

Loading…