Potassium Phosphate, Tribasic → 6,7-Difluoro-2-(4-methylpyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 1843956Notes

Reaction equation

HRID 1843956 reaction equation
ClC1C=[C:10]2[C:5]([CH2:6][CH2:7][N:8](C3C=NC=CC=3)[C:9]2=O)=[CH:4]C=1.[F:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[F:30])[C:26](=[O:31])[NH:25][CH2:24][CH2:23]2.IC1C=NC=CC=1C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.O1CCOCC1>[F:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[F:30])[C:26](=[O:31])[N:25]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:5]=1[CH3:4])[CH2:24][CH2:23]2

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 144235133-Iodo-4-methylpyridineHCID 569427267-Chloro-2-pyridin-3-yl-3,4-dihydro-2H-isoquinolin-1-oneHCID 899639446,7-difluoro-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 569430506,7-Difluoro-2-(4-methylpyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 24%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

Using analogous conditions as described in example 1 for the preparation of Compound 1A, 6,7-difluoro-3, 4-dihydroisoquinolin-1(2H)-one (I-49d: 300 mg, 1.6393 mmol) was reacted with 3-iodo-4-methyl-pyridine (359 mg, 1.6393 mmol), 1, 4-dioxane (15 mL), copper iodide (31.2 mg, 0.1639 mmol), trans-N,N′-dimethyl-cyclohexyl-1, 2-diamine (77.3 mL, 0.4917 mmol) and potassium phosphate (868.8 mg, 4.0982 mmol) to afford the crude product. Purification by column chromatography on silica gel (80% ethylacetate in hexane) afforded 110 mg of the product (24% yield).

Workup

  1. customto afford the crude product
  2. customPurification by column chromatography on silica gel (80% ethylacetate in hexane)

Sources & evidence

ORD record
ord-04226e07bd5b494ba08aac6c7452208c
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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