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 883057ノート

反応式

HRID 883057 の反応式
[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]

参加物

8

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 8471Triethylamine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-87492a17dbd64a10a6ef98757f1c8d36
出典データセット
uspto-grants-2012_08
特許番号
US08236828B2

反応ノート

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