Chlorosuccinimide → 3-amino-N-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6-dimethyl-phenyl}-4-cyano-benzamide

HRID 883057Notes

Reaction equation

HRID 883057 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH:6]=[N:7][OH:8])=[CH:4][CH:3]=1.ClN1C(=O)CCC1=O.[NH2:19][C:20]1[CH:21]=[C:22]([CH:40]=[CH:41][C:42]=1[C:43]#[N:44])[C:23]([NH:25][C:26]1[C:31]([CH3:32])=[CH:30][C:29]([C:33]([C:35]([F:38])([F:37])[F:36])=[CH2:34])=[CH:28][C:27]=1[CH3:39])=[O:24]>CN(C)C=O.O.C(OCC)(=O)C.C(N(CC)CC)C>[NH2:19][C:20]1[CH:21]=[C:22]([CH:40]=[CH:41][C:42]=1[C:43]#[N:44])[C:23]([NH:25][C:26]1[C:27]([CH3:39])=[CH:28][C:29]([C:33]2([C:35]([F:36])([F:37])[F:38])[O:8][N:7]=[C:6]([C:5]3[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH2:34]2)=[CH:30][C:31]=1[CH3:32])=[O:24]

Participants

8

Reactant 3

HCID 31398ChlorosuccinimideHCID 2191584-Chloro-benzaldehyde oximeHCID 594559073-amino-4-cyano-N-[2,6-dimethyl-4-(1-trifluoromethyl-vinyl)-phenyl]-benzamide

Product 1

HCID 594559083-amino-N-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6-dimethyl-phenyl}-4-cyano-benzamideYield 59%

Reagents, catalysts & solvents 4

HCID 8471TriethylamineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-Chloro-benzaldehyde oxime (6.64 g, 42.70 mmol) and N-chlorosuccinimide (“NCS”) (5.70 g, 42.70 mmol) were dissolved in N,N-dimethylformamide (40 ml). The reaction mixture was stirred at ambient temperature for 90 minutes. A solution of 3-amino-4-cyano-N-[2,6-dimethyl-4-(1-trifluoromethyl-vinyl)-phenyl]-benzamide (4.4 g, 12.20 mmol) (Example I5) and triethylamine (5.95 mL, 0.66 mmol) in N,N-dimethylformamide (40 ml) was added and the reaction mixture was stirred at ambient temperature for 18 hours. The reaction mixture was diluted with water (500 ml) and ethyl acetate (500 ml) and the phases were separated. The organic phase was washed twice with water and the aqueous phases were extracted once with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 3:1) to give 3-amino-N-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-5-yl]-2,6-dimethyl-phenyl}-4-cyano-benzamide (3.67 g, 59% yield). LC/MS (Method A): 513 (MH+); RT: 2.04. 1H-NMR (CDCl3, 400 MHz): 7.62 (m, 3H), 7.45 (d, 1H), 7.40 (m, 2H), 7.36 (s, 2H), 7.31 (s, 1H), 7.18 (d, 1H), 4.63 (s, 2H), 4.08 (d, 1H), 3.76 (d, 1H), 2.30 (s, 6H) ppm.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 18 hours
  2. customthe phases were separated
  3. washThe organic phase was washed twice with water
  4. extractionthe aqueous phases were extracted once with ethyl acetate
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-87492a17dbd64a10a6ef98757f1c8d36
Source dataset
uspto-grants-2012_08
Patent number
US08236828B2

Reaction notes

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