3-Bromopyridine → 7-Chloro-2-pyridin-3-yl-3,4-dihydro-2H-isoquinolin-1-one

HRID 1843820Notes

Reaction equation

HRID 1843820 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1.[Cl:15][C:16]1[CH:25]=[C:24]2[C:19]([CH2:20][CH2:21][NH:22][C:23]2=[O:26])=[CH:18][CH:17]=1.Br[C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>C(Cl)(Cl)Cl.[Cu](I)I.CO>[Cl:15][C:16]1[CH:25]=[C:24]2[C:19]([CH2:20][CH2:21][N:22]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[C:23]2=[O:26])=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 122863-BromopyridineHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 186723977-Chloro-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 569427267-Chloro-2-pyridin-3-yl-3,4-dihydro-2H-isoquinolin-1-oneYield 42.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 887MethanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
110 °C

Procedure

Copper iodide (15.6 mg, 0.0824 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (28.3 mg, 0.2472 mmol) and potassium phosphate (437.3 mg, 2.0604 mmol) were added to 1,4-dioxane (20 mL) degassed with argon for 30 minutes. The reaction mixture was purged with argon for a further 20 minutes followed by the addition of 7-chloro-3,4-dihydro-2H-isoquinolin-1-one (I-1d: 150 mg, 0.82417 mmol) and 3-bromo-pyridine (88.9 mL, 0.9065 mmol). The reaction mixture was heated to reflux at 110° C. for 12 hours. The reaction was monitored by TLC (10% methanol in CHCl3). The reaction mixture was filtered and the filtrate was concentrated. Purification by column chromatography on silica gel (10% methanol in CHCl3) afforded 90 mg of the product (42.2% yield).

Workup

  1. customdegassed with argon for 30 minutes
  2. customThe reaction mixture was purged with argon for a further 20 minutes
  3. temperatureThe reaction mixture was heated
  4. filtrationThe reaction mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. customPurification by column chromatography on silica gel (10% methanol in CHCl3)

Sources & evidence

ORD record
ord-ac2e280a77344802b6ce6e13aac6b2eb
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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