Dimethylformamide → N-(1-Cyanoisoquinolin-5-yl)-N'-[4(trifluoromethyl)benzyl]urea

HRID 1181494Notes

Reaction equation

HRID 1181494 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([NH:12][C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[O:14])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:27][N:28](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:2]1[C:11]2[C:6](=[C:7]([NH:12][C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[O:14])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1)#[N:28]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 99997771-(1-Chloro-isoquinolin-5-yl)-3-(4-trifluoromethyl-benzyl)-urea

Product 1

HCID 69522104N-(1-Cyanoisoquinolin-5-yl)-N'-[4(trifluoromethyl)benzyl]ureaYield 65.6%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×

Procedure

To a solution of N-(1-chloroisoquinolin-5-yl)-N′-[4-(trifluoromethyl)benzyl]urea (Example 69) (250 mg, 0.7 mmol) in DMF (5 ml) was added zinc cyanide (43 mg, 0.37 mmol) and tetrakis(triphenylphosphine)palladium (76 mg, 0.07 mmol). The reaction was heated at 80° C., under an atmosphere of nitrogen, for 72 hr, with the addition of extra tetrakis(triphenylphosphine)palladium (76 mg, 0.07 mmol) after 16 hr. Reaction mixture was quenched with water and extracted with ethyl acetate (3×5 ml), dried over MgSO4 and evaporated. The residue was purified by flash column chromatography using an eluant system of 3% methanol/97% DCM increasing to 5% MeOH/95% DCM. Recrystallisation in ethanol of a small portion of product gave a pure sample of the title compound (50 mg, 65.6%). m/z (ES+) 371, 373 (M+H)+.

Workup

  1. customReaction mixture
  2. customwas quenched with water
  3. extractionextracted with ethyl acetate (3×5 ml)
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was purified by flash column chromatography
  7. customRecrystallisation in ethanol of a small portion of product

Sources & evidence

ORD record
ord-c88852c606a94588ae1f91b7de276238
Source dataset
uspto-grants-2007_10
Patent number
US07285563B2

Reaction notes

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