4-(Trifluoromethyl)phenyl isocyanate → N-{6-[2-chloro-4-fluoro-5-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-7-cyano-1,3-benzothiazol-2-yl}cyclopropanecarboxamide

HRID 1097484ノート

反応式

HRID 1097484 の反応式
[NH2:1][C:2]1[C:3]([F:27])=[CH:4][C:5]([Cl:26])=[C:6]([CH:25]=1)[O:7][C:8]1[CH:22]=[CH:21][C:11]2[N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[S:14][C:10]=2[C:9]=1[C:23]#[N:24].[N:28]([C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=1)=[C:29]=[O:30]>CN(C)C=O.C(OCC)(=O)C>[Cl:26][C:5]1[CH:4]=[C:3]([F:27])[C:2]([NH:1][C:29](=[O:30])[NH:28][C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:38])([F:40])[F:39])=[CH:33][CH:32]=2)=[CH:25][C:6]=1[O:7][C:8]1[CH:22]=[CH:21][C:11]2[N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[S:14][C:10]=2[C:9]=1[C:23]#[N:24]

参加物

5

反応物 2

HCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 86644692N-[6-(5-amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

生成物 1

HCID 59454471N-{6-[2-chloro-4-fluoro-5-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-7-cyano-1,3-benzothiazol-2-yl}cyclopropanecarboxamide収率 52.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

N-[6-(5-Amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (150 mg, 0.372 mmol) produced in Example 23(vi) was dissolved in N,N-dimethylformamide (1.5 mL), 1-isocyanato-4-(trifluoromethyl)benzene (69 μL, 0.484 mmol) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (10 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→45/95), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from acetone/n-hexane to give the title compound (115 mg, 52%) as a white powder.

後処理

  1. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (5 mL) and saturated brine (5 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationInsoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→45/95)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was recrystallized from acetone/n-hexane

出典と根拠

ORDレコード
ord-fa2b4830249b47e1a48cb31da204d5d9
出典データセット
uspto-grants-2012_03
特許番号
US08143258B2

反応ノート

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