Sodium hydride → HCID 68283889, compound

HRID 2408608Notes

Reaction equation

HRID 2408608 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:25]=[CH:24][C:23]([C:26]2([CH3:29])[CH2:28][O:27]2)=[CH:22][N:21]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([CH2:29][C:26]([C:23]3[CH:22]=[N:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=3)([OH:27])[CH3:28])[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 86677139HCID 86677139, compound

Product 1

HCID 68283889HCID 68283889, compoundYield 20.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (500 mg, 2.5 mmol) was dissolved in 5 mL DMF and stirred for 10 min at RT. Sodium hydride (300 mg, 7.5 mmol) was added portionwise at 0° C. and the reaction mixture was stirred for 10 min. 2-Methoxy-5-(2-methyl-oxiranyl)-pyridine (566 mg, 3.75 mmol) was diluted in DMF (2 mL) and added dropwise at the same temperature and stirred for 12 h. After consumption of starting material, the reaction mixture was quenched with ice water and extracted with EtOAc (3×30 mL). The combined organic layer was washed with water (7×30 mL), dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography over silica gel (eluent: 15% MeOH in DCM) and further crystallized in ether-hexane to obtain 190 mg of 1-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-(6-methoxy-pyridin-3-yl)-propan-2-ol. 1H NMR (CDCl3, freebase) δ (ppm): 8.22 (s, 1H), 7.5 (d, 1H), 7.1 (s, 1H), 7.0 (d, 1H), 6.83 (d, 1H), 6.5 (d, 1H), 4.1 (m, 2H), 3.91 (s, 3H), 3.5 (m, 2H), 2.63-2.81 (m, 4H), 2.41 (s, 3H), 2.39 (s, 3H), 1.58 (s, 3H). Separation by chiral HPLC provides enantiomers 64a and 64b.

Workup

  1. stirringthe reaction mixture was stirred for 10 min
  2. additionadded dropwise at the same temperature
  3. stirringstirred for 12 h
  4. customAfter consumption of starting material
  5. customthe reaction mixture was quenched with ice water
  6. extractionextracted with EtOAc (3×30 mL)
  7. washThe combined organic layer was washed with water (7×30 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography over silica gel (eluent: 15% MeOH in DCM)
  11. customfurther crystallized in ether-hexane

Sources & evidence

ORD record
ord-7a8162b42008461db18a14103aaa0c2c
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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