Potassium Phosphate, Tribasic → 8-fluoro-7-(trifluoromethyl)-2-(4-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 1844043Notes

Reaction equation

HRID 1844043 reaction equation
[F:1][C:2]1[C:3]([C:13]([F:16])([F:15])[F:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.Br[C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[C:24]([F:27])([F:26])[F:25].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.O1CCOCC1>[F:1][C:2]1[C:3]([C:13]([F:16])([F:14])[F:15])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[C:24]([F:27])([F:26])[F:25])[CH2:8][CH2:7]2

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 199372633-Bromo-4-(trifluoromethyl)pyridineHCID 668020098-fluoro-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 871583218-fluoro-7-(trifluoromethyl)-2-(4-(trifluoromethyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 15.4%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

8-Fluoro-7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-one (I-77d: 100 mg, 0.4288 mmol) was reacted with 3-bromo-4-(trifluoromethyl)-pyridine (120 mg, 0.5575 mmol), 1,4-dioxane (5 mL), copper iodide (8.1 mg, 0.0428 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (6.1 mg, 0.0428 mmol) and potassium phosphate (273 mg, 1.2866 mmol) to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3), followed by preparative HPLC afforded 25 mg of the product (15.4% yield).

Workup

  1. customto afford the crude product
  2. customPurification by column chromatography on silica gel (2% methanol in CHCl3)

Sources & evidence

ORD record
ord-e085138158ee4239a2875df5a622da33
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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