Potassium Hydroxide → HCID 59455277, compound

HRID 1401613Notes

Reaction equation

HRID 1401613 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=3)(O)[CH3:13])[C:6]3[CH2:22][CH2:23][N:24]([CH3:26])[CH2:25][C:5]=3[C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[OH-].[K+]>C(Cl)Cl.CN(C=O)C.CN1C(=O)CCC1.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:11]=[C:12](/[C:15]3[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=3)\[CH3:13])[C:6]3[CH2:22][CH2:23][N:24]([CH3:26])[CH2:25][C:5]=3[C:4]=2[CH:3]=1

Participants

8

Reactant 3

HCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 68486810HCID 68486810, compound

Product 1

HCID 59455277HCID 59455277, compoundYield 14.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(2-methylpyridin-4-yl)propan-2-ol (150 mg, 0.4 mmol) in DCM (12 mL) and DMF (2 drops) was stirred at 0-10° C. Thionyl chloride (145 mg, 1.2 mmol) diluted in DCM (8 mL) was added dropwise and the RM stirred at RT for 2 h. The solvent was removed and the residue dried to obtain foamy solid. The solid was dissolved in NMP (2 mL), stirred for 5 min. Powdered KOH (141 mg, 2.52 mmol) was added to the reaction mixture, which was heated at 80° C. for 1 h. After completion of reaction, the reaction mixture was poured in water and the compound extracted with DCM (3×50 mL). The organic layer was washed with water, dried over sodium sulfate and concentrated under vacuum to obtain the crude product which was purified by reverse phase HPLC to obtain 20 mg of 8-chloro-2,3,4,5-tetrahydro-2-methyl-5-((E)-2-(2-methylpyridin-4-yl)prop-1-enyl)-1H-pyrido[4,5-b]indole as the free base. The free base was converted to HCl salt by treating with ethanolic HCl. 1H NMR (CD3OD, Di-HCl salt) δ (ppm): 8.70 (d, 1H), 8.20 (s, 1H), 8.15 (d, 1H), 7.72 (s, 1H), 7.60 (s, 1H), 7.25 (m, 2H), 4.70 (m, 1H), 4.40 (m, 1H), 3.80 (m, 1H), 3.60 (m, 1H), 3.20 (m, 2H), 3.10 (s, 3H), 2.82 (s, 3H), 2.10 (s, 3H).

Workup

  1. additionwas added dropwise
  2. customThe solvent was removed
  3. customthe residue dried
  4. customto obtain foamy solid
  5. stirringstirred for 5 min
  6. temperaturewas heated at 80° C. for 1 h
  7. customAfter completion of reaction
  8. extractionthe compound extracted with DCM (3×50 mL)
  9. washThe organic layer was washed with water
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under vacuum
  12. customto obtain the crude product which
  13. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-f210c914f77a4b51bd2c794869b584ff
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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