Benzyl Chloride → HCID 11150458, compound

HRID 574378Notes

Reaction equation

HRID 574378 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.[CH2:16](Cl)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[OH-].[Na+]>C(NC(C)C)(C)C>[CH2:16]([N:6]1[C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=2[C:4]2[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]1=2)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 7503Benzyl ChlorideHCID 14798Sodium HydroxideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-

Product 1

HCID 11150458HCID 11150458, compoundYield 13.8%

Reagents, catalysts & solvents 1

HCID 7912DiisopropylamineSolvent

Procedure

Preparation of the title compound was carried out according to General Method 5. 2,3,4,5-Tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (Example 1) (100 mg, 0.5 mmol) and benzyl chloride (0.11 ml, 0.9 mmol) in diisopropylamine (2 mL) were heated at 80° C. for 12 h. The contents were basified with 1N NaOH and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated. The resulting crude product was purified by silica gel chromatography (230-400 mesh) using methanol-dichloromethane gradient followed by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL) to obtain 20 mg of 5-benzyl-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole as a trifluoroacetate salt.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe resulting crude product was purified by silica gel chromatography (230-400 mesh)
  5. customfollowed by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL)

Sources & evidence

ORD record
ord-a2da2e36dbf6408f8c989f4e0f3adf9b
Source dataset
uspto-grants-2015_05
Patent number
US09034880B2

Reaction notes

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