Dimethylformamide → (E)-2,8-dimethyl-5-(2-(pyridin-4-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400398Notes

Reaction equation

HRID 1400398 reaction equation
[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6]([CH2:14][C:15]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)(O)[CH3:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.CN(C=O)C.S(Cl)(Cl)=O.CO.C(Cl)Cl>C(Cl)Cl>[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6](/[CH:14]=[C:15](/[C:18]3[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=3)\[CH3:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 21226129Dichloromethane methanolHCID 497797781-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-4-yl)propan-2-ol

Product 1

HCID 59454985(E)-2,8-dimethyl-5-(2-(pyridin-4-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 29.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-4-yl)propan-2-ol (6 g, 17.91 mmol) was dissolved in DCM (75 mL). DMF (1 mL) was added and the reaction mixture was cooled to 0° C. Thionyl chloride (3.89 mL, 53.73 mmol) was diluted with DCM (75 mL) and added to the above reaction mixture dropwise. The reaction mixture was stirred at RT for 3 h. Progress of the reaction was monitored by TLC (10% MeOH-DCM). Upon completion of the reaction, the reaction mixture was evaporated to dryness and the residue was basified with saturated aqueous NaHCO3 with cooling. The product was extracted with EtOAc, the organic layer was washed with water; dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel chromatography (100-200 mesh) eluting with 2% MeOH-DCM to obtain 1.7 g of product as the free base. 1H NMR (DMSO, Oxalate salt) δ (ppm): 8.70 (s,1H), 7.69 (d,2H), 7.46 (m,1H), 7.31 (s,1H), 7.13 (d,1H), 7.06 (m,1H), 6.85 (s,1H), 3.70 (m,2H), 3.10 (m,2H), 3.0 (s,3H), 2.66 (m,1H), 2.40 (s,3H), 2.20 (m,2H), 1.90 (m,2H).

Workup

  1. additionadded to the above reaction mixture dropwise
  2. customUpon completion of the reaction
  3. customthe reaction mixture was evaporated to dryness
  4. temperaturewith cooling
  5. extractionThe product was extracted with EtOAc
  6. washthe organic layer was washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (100-200 mesh)
  10. washeluting with 2% MeOH-DCM

Sources & evidence

ORD record
ord-9e007d1e785f48d29577ced6128634a4
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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