Sodium hydride → (2E)-N-5-isoquinolinyl-3-[4-(trifluoromethyl)phenyl]-2-butenamide

HRID 585975Notes

Reaction equation

HRID 585975 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6](/[C:9](/[CH3:14])=[CH:10]/[C:11]([OH:13])=O)=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[CH:27][N:28]=[CH:29]2.[H-].[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH:29]1[C:30]2[C:25](=[C:24]([NH:23][C:11](=[O:13])/[CH:10]=[C:9](/[C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:16])[F:15])=[CH:8][CH:7]=3)\[CH3:14])[CH:33]=[CH:32][CH:31]=2)[CH:26]=[CH:27][N:28]=1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 707665-AminoisoquinolineHCID 287914333-[4-(Trifluoromethyl)phenyl]but-2-enoic acid

Product 1

HCID 22032631(2E)-N-5-isoquinolinyl-3-[4-(trifluoromethyl)phenyl]-2-butenamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

The product from Example 142C (0.23 g, 1.00 mmol) in CH2Cl2 (5 mL) was treated with oxalyl chloride (0.15 g, 1.2 mmol), 1 drop of DMF, and stirred at ambient temperature for 45 minutes. The mixture was treated with a solution of 5-aminoisoquinoline (0.14 g, 1.0 mmol) and 98% NaH (0.048 g, 1.2 mmol) in DMF (5 mL) prepared separately by stirring for 45 minutes. The resulting mixture was stirred for 15 minutes, poured into water, and extracted with CH2Cl2. The organic phase was dried (MgSO4), evaporated, and the residue triturated with diethyl ether. The solid was dried under reduced pressure to provide the title compound. 1H NMR (300 MHz, d6-DMSO) 2.61 (s, 3H), 2.73 (s, 0.45H, DMF)), 2.89 (s, 0.45H (DMF)), 6.82 (br s, 1H), 7.70 (t, 1H), 7.83 (s, 4H), 7.95 (d, 1H), 8.04 (d, 1H), 8.21 (d, 1H), 8.56 (d, 1H), 9.33 (s, 1H), 10.20 (s, 1H); MS (ESI+) 357 (M+H)+; Elemental: Calculated for C20H15N2OF3.HCl.0.15C3H7NO: C, 66.87, H, 4.40, N, 8.20; Found: C, 66.83, H, 4.20, N, 8.27.

Workup

  1. customprepared separately
  2. stirringby stirring for 45 minutes
  3. stirringThe resulting mixture was stirred for 15 minutes
  4. extractionextracted with CH2Cl2
  5. dry with materialThe organic phase was dried (MgSO4)
  6. customevaporated
  7. customthe residue triturated with diethyl ether
  8. customThe solid was dried under reduced pressure

Sources & evidence

ORD record
ord-9453a401e02640cd84586ee729c12530
Source dataset
uspto-grants-2005_08
Patent number
US06933311B2

Reaction notes

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