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

HRID 1843971Notes

Reaction equation

HRID 1843971 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][C:10]2=[O:13])=[CH:5][CH:4]=1.Br[C:17]1[CH:18]=[N:19][CH:20]=[CH:21][C:22]=1[CH:23]([O:26][CH3:27])[O:24][CH3:25].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.O1CCOCC1>[CH3:25][O:24][CH:23]([O:26][CH3:27])[C:22]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[N:9]1[CH2:8][CH2:7][C:6]2[C:11](=[CH:12][C:3]([C:2]([F:1])([F:14])[F:15])=[CH:4][CH:5]=2)[C:10]1=[O:13]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 207151453-Bromo-4-(dimethoxymethyl)pyridineHCID 668015937-(Trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 668035582-(4-(dimethoxymethyl)pyridin-3-yl)-7-(trifluoromethyl)-3,4-dihydroisoquinolin-1(2H)-oneYield 98.8%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

Using analogous conditions as described for the preparation of Example 1A above, 7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-one (I-4-d: 505.4 mg, 2.3503 mmol) was reacted with 3-Bromo-4-dimethoxymethyl-pyridine (I-52a: 600 mg, 2.5854 mmol), 1,4-dioxane (20 mL), copper iodide (44.6 mg, 0.2348 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (80.9 mg, 0.7052 mmol) and potassium phosphate (1.49 g, 7.0507 mmol) to afford the crude product. Purification by column chromatography on silica gel (1% methanol in CHCl3) afforded 850 mg of the product (98.8% yield).

Workup

  1. customas described for the preparation of Example 1A above
  2. customto afford the crude product
  3. customPurification by column chromatography on silica gel (1% methanol in CHCl3)

Sources & evidence

ORD record
ord-6f259627d6cd48959c39072f4dc87b60
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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