Potassium Hydroxide → (E)-6-fluoro-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401502Notes

Reaction equation

HRID 1401502 reaction equation
[F:1][C:2]1[C:10]2[N:9]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)(O)[CH3:13])[C:8]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[OH-].[K+]>S(Cl)(Cl)=O.O>[F:1][C:2]1[C:10]2[N:9](/[CH:11]=[C:12](/[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)\[CH3:13])[C:8]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 497795251-(6-Fluoro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-4-yl)propan-2-ol

Product 1

HCID 59455177(E)-6-fluoro-2-methyl-5-(2-(pyridin-4-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 24386Thionyl ChlorideSolvent

Procedure

1-(6-Fluoro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-4-yl)propan-2-ol (510 mg, 1.5 mmol) was dissolved in thionylchloride (5 mL) and stirred at RT for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in N-methyl-2-pyrrolidone (3 mL) and stirred for 5 min. at RT. Powdered KOH (616 mg, 10 mmol) was added, and the stirring was continued for additional 10 min. The reaction mixture was heated at 100° C. for 2 h. The progress of reaction was monitored by TLC and NMR. The reaction mixture was diluted with water and extracted with EtOAc, washed with water, concentrated to obtain the crude product which was purified by HPLC. 1H NMR (DMSO-d6, TFA salt) δ (ppm): 8.80 (d, 2H), 8.0 (d, 2H), 7.70 (s, 1H), 7.40 (d, 1H), 7.30 (m, 1H), 7.10 (m, 1H), 4.80 (m, 1H), 4.30 (m, 1H), 3.80 (m, 2H), 3.10 (m, 2H), 3.0 (s, 3H), 2.0 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in N-methyl-2-pyrrolidone (3 mL)
  3. stirringstirred for 5 min. at RT
  4. waitthe stirring was continued for additional 10 min
  5. temperatureThe reaction mixture was heated at 100° C. for 2 h
  6. customThe progress of reaction
  7. extractionextracted with EtOAc
  8. washwashed with water
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-60052d79453448edaa940235c74eb0c6
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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