Potassium Hydroxide → 3,6-dimethyl-9-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c']dipyridine

HRID 1630604Notes

Reaction equation

HRID 1630604 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:10]3[CH2:11][N:12]([CH3:15])[CH2:13][CH2:14][C:9]=3[NH:8][C:5]2=[N:6][CH:7]=1.[OH-].[K+].[F:18][C:19]([F:29])([F:28])[C:20]1[CH:25]=[CH:24][C:23]([CH:26]=[CH2:27])=[CH:22][N:21]=1>CN1C(=O)CCC1.O>[CH3:1][C:2]1[CH:3]=[C:4]2[C:10]3[CH2:11][N:12]([CH3:15])[CH2:13][CH2:14][C:9]=3[N:8]([CH2:27][CH2:26][C:23]3[CH:22]=[N:21][C:20]([C:19]([F:29])([F:18])[F:28])=[CH:25][CH:24]=3)[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 574168485-Ethenyl-2-(trifluoromethyl)pyridineHCID 687572963,6-dimethyl-6,7,8,9-tetrahydro-5H-1,6,9-triaza-fluorene

Product 1

HCID 578763653,6-dimethyl-9-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c']dipyridineYield 21.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 3,6-dimethyl-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c′]dipyridine (201 mg, 1.0 mmol) in NMP (3 mL) was added powdered KOH (392 mg, 7.0 mmol). After stirring for 10 min at RT, 2-(trifluoromethyl)-5-vinylpyridine (346 mg, 2.0 mmol) was added to the reaction mixture and stirring continued for another 3 h. The progress of reaction was monitored by TLC and NMR. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (3×20 mL). The organic layer was washed with water (5×20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 3,6-dimethyl-9-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:4,5-c′]dipyridine (80 mg). 1H NMR (CDCl3, TFA salt) δ (ppm): 8.38 (s, 1H), 8.0 (s, 1H), 7.5 (d, 2H), 7.4 (d, 1H), 4.4 (t, 2H), 3.58 (s, 2H), 3.2 (t, 2H), 2.68 (t, 2H), 2.5 (t, 2H), 2.47 (s, 3H), 2.38 (s, 3H).

Workup

  1. stirringstirring
  2. waitcontinued for another 3 h
  3. customThe progress of reaction
  4. extractionextracted with EtOAc (3×20 mL)
  5. washThe organic layer was washed with water (5×20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude material, which
  9. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-36b5bfffbc0f4ee9b87cce741a9a0cfb
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

Loading…