Sodium hydride → 1-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-3-yl)propan-2-ol

HRID 2408588Notes

Reaction equation

HRID 2408588 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][C:19]1([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH2:21][O:20]1>CN(C=O)C>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([CH2:18][C:19]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)([OH:20])[CH3:21])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 230811803-(2-Methyloxiran-2-yl)pyridine

Product 1

HCID 578760881-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-3-yl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (290 mg, 1.4 mmol) in DMF (6 mL) was added sodium hydride (38 mg, 1.6 mmol) and the solution was stirred at 120° C. for 1 h. The reaction mixture was cooled to 0° C. and 3-(2-methyloxiran-2-yl)pyridine (400 mg, 2.96 mmol) was added dropwise over a period of 5 min. The reaction mixture was stirred at 120° C. for 2 h, quenched with ice-water (15 mL) and extracted with EtOAc (60 mL). The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash column chromatography (5-15% MeOH/EtOAc) to yield 1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-3-yl)propan-2-ol. Separation by chiral HPLC provided enantiomers 5a and 5b. 1H NMR (CDCl3, freebase) δ (ppm): 8.79 (s, 1H), 8.42 (d, 1H), 7.56 (d, 1H), 7.04 (s, 1H), 6.9 (m, 2H), 6.8 (d, 1H), 4.17 (dd, 2H), 3.42 (s, 2H), 2.8 (t, 2H), 2.62 (t, 2H), 2.42 (s, 3H), 2.39 (s, 3H), 1.61 (s, 3H). Optical rotations: Compound No. 5a, (−) 39.27 (c 0.43, Chloroform, 99.69% HPLC purity); Compound No. 5b, (+) 58.97 (c 0.58, Chloroform, 99.49% HPLC purity).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringThe reaction mixture was stirred at 120° C. for 2 h
  3. customquenched with ice-water (15 mL)
  4. extractionextracted with EtOAc (60 mL)
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography (5-15% MeOH/EtOAc)

Sources & evidence

ORD record
ord-de4f01881e114d47a115325d9281478d
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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