Trifluoroacetic acid → N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476375ノート

反応式

HRID 476375 の反応式
COC1C=CC(C[NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]4([C:28]([NH:30][C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)=[O:29])[CH2:27][CH2:26]4)=[O:24])=[C:18]([F:38])[CH:17]=3)[CH:12]=[CH:11][N:10]=2)=CC=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]3([C:28]([NH:30][C:31]4[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=4)=[O:29])[CH2:27][CH2:26]3)=[O:24])=[C:18]([F:38])[CH:17]=2)[CH:12]=[CH:11][N:10]=1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 66604557N-(4-(2-(4-methoxybenzylamino)pyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

生成物 1

HCID 59596943N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 42.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of N-(4-(2-(4-methoxybenzylamino)pyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (160 mg, 0.29 mmol) in CH2Cl2 (0.2 mL) was treated with trifluoroacetic acid (0.4 mL, 5.26 mmol) and the resultant mixture was stirred overnight at RT. The reaction mixture was concentrated to dryness and the residue was purified by reverse-phase silica gel chromatography (25-95% acetonitrile in water, 0.1% TFA). The desired fractions were partitioned between saturated aqueous NaHCO3 and EtOAc. The organics were washed with saturated aqueous NaHCO3, water, and brine and were dried over Na2SO4 and concentrated in vacuo to provide N-(4-(2-aminopyridin-4-yloxy)-2-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (52 mg, 39% yield). MS (ESI) m/z: 425.1 (M+H+).

後処理

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue was purified by reverse-phase silica gel chromatography (25-95% acetonitrile in water, 0.1% TFA)
  3. customThe desired fractions were partitioned between saturated aqueous NaHCO3 and EtOAc
  4. washThe organics were washed with saturated aqueous NaHCO3, water, and brine
  5. dry with materialwere dried over Na2SO4
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-fb65a14fee9c4a0ca829b9a1e0db0c30
出典データセット
uspto-grants-2014_01
特許番号
US08637672B2

反応ノート

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