Potassium Phosphate, Tribasic → HCID 53372879, compound

HRID 715152Notes

Reaction equation

HRID 715152 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.Br[C:17]1[CH:18]=[CH:19][C:20]([C:23]([F:26])([F:25])[F:24])=[N:21][CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O>CN(C=O)C.O.[Cu]I>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([C:17]3[CH:22]=[N:21][C:20]([C:23]([F:26])([F:25])[F:24])=[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

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 27611975-Bromo-2-(trifluoromethyl)pyridine

Product 1

HCID 53372879HCID 53372879, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.4 g, 2 mmol), 5-bromo-2-trifluoromethyl-pyridine (1.356 g, 6 mmol), K3PO4 (1.272 g, 6 mmol), CuI (38 mg, 0.2 mmol) and L-Proline (70 mg, 0.4 mmol) in dry DMF (5 mL) was stirred at 150° C. for 4 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by column chromatography using silica (100-200 mesh) and 3% MeOH:DCM to yield 2,8-dimethyl-5-(6-trifluoromethyl-pyridin-3-yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole as an off white solid (150 mg). 1H NMR (HCl salt, CD3OD) d (ppm): 8.85 (s, 1H), 8.2 (d, 1H), 8.1 (d, 1H), 7.4 (s, 1H), 7.2 (d, 1H), 7.1 (d, 1H), 4.8 (m, 1H), 4.4 (m, 1H), 3.9-3.85 (m, 1H), 3.6-3.59 (m, 1H), 3.25-3.2 (m, 1H), 3.2 (s, 3H), 3.1-3.0 (m, 1H), 2.41 (s, 3H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford crude material, which
  5. customwas purified by column chromatography

Sources & evidence

ORD record
ord-49069d047f644c3b85e8660f18520fc6
Source dataset
uspto-grants-2015_11
Patent number
US09187471B2

Reaction notes

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