Potassium Hydroxide → HCID 46224945, compound

HRID 1401641Notes

Reaction equation

HRID 1401641 reaction equation
[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6]([CH:14]([CH3:23])[CH:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)O)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.S(Cl)(Cl)=O.[OH-].[K+]>C(Cl)Cl.CN(C=O)C.CN1C(=O)CCC1.O>[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6](/[C:14](/[CH3:23])=[CH:15]\[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6](/[C:14](/[CH3:23])=[CH:15]/[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

9

Reactant 3

HCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 59455003HCID 59455003, compound

Product 2

HCID 46224945HCID 46224945, compoundHCID 59455062HCID 59455062, compound

Reagents, catalysts & solvents 4

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

Procedure

A solution of 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-phenyl-propan-1-ol (100 mg, 0.29 mmol) in DCM (5 mL) and DMF (2 drops) was stirred at 0-10° C. Thionyl chloride (0.8 mL, 11.02 mmol) was added and the reaction mixture stirred at RT for 2 h. The solvent was removed under vacuum to obtain the crude as a dark brown solid, which was dissolved in NMP (2 mL) and stirred for 5 min. Powdered KOH (167 mg, 2.99 mmol) was added to the reaction mixture and the contents heated at 85° C. for 45 min. After completion of reaction, the reaction mixture was poured in water and the desired compound extracted with EtOAc (3×100 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated under vacuum to obtain the crude product (40 mg) which was purified by reverse phase HPLC to yield (Z)-2,8-Dimethyl-5-(1-methyl-2-phenyl-vinyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (10 mg) and (E)-2,8-Dimethyl-5-(1-methyl-2-phenyl-vinyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (12 mg) which were converted to their respective HCl salts. 1H NMR (CDCl3, free base) δ (ppm): 7.40 (m, 3H), 7.30-7.20 (m, 4H), 6.98 (d, 1H), 6.60 (s, 1H), 3.76 (s, 2H), 2.60 (s, 3H), 2.30 (s, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. customto obtain the crude as a dark brown solid, which
  3. stirringstirred for 5 min
  4. temperaturethe contents heated at 85° C. for 45 min
  5. customAfter completion of reaction
  6. extractionthe desired compound extracted with EtOAc (3×100 mL)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customto obtain the crude product (40 mg) which
  10. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-55ae362c4afb4099a5eaa1da312967c9
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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