Potassium Phosphate, Tribasic → 8-Fluoro-2-(4-methyl-pyridin-3-yl)-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-one

HRID 1843951Notes

Reaction equation

HRID 1843951 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.I[C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>[Cu]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[CH3:24])[CH2:8][CH2:7]2

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 144235133-Iodo-4-methylpyridineHCID 668020098-fluoro-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 569430488-Fluoro-2-(4-methyl-pyridin-3-yl)-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-oneYield 4.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

8-Fluoro-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-one (I-47d: 150 mg, 0.643 mmol) was reacted with 3-iodo-4-methyl-pyridine (140.98 mg, 0.643 mmol), K3PO4 (346.76 mg, 1.607 mmol), trans-N,N′-dimethyl-cyclohexane-1, 2-diamine (0.03 mL, 0.192 mmol), CuI (12.24 mg, 0.0643 mmol) and 1,4-dioxane (10 mL). The resulting mixture was refluxed for 16 hours at 110° C. to afford the crude product. Purification by column chromatography on silica gel (40% ethylacetate in hexane) followed by preparative HPLC afforded 10 mg of the product (4.8% yield).

Workup

  1. customto afford the crude product
  2. customPurification by column chromatography on silica gel (40% ethylacetate in hexane)

Sources & evidence

ORD record
ord-8b5bf56f300743459b6580267eb7427d
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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