1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → Regorafenib

HRID 475440ノート

反応式

HRID 475440 の反応式
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:19])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][C:22]=1[C:30]([F:33])([F:32])[F:31]>C1(C)C=CC=CC=1>[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:28]([NH:27][C:24]3[CH:25]=[CH:26][C:21]([Cl:20])=[C:22]([C:30]([F:32])([F:31])[F:33])[CH:23]=3)=[O:29])=[C:14]([F:19])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4]

参加物

4

反応物 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

生成物 1

HCID 11167602Regorafenib収率 47.1%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a solution of 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide (177 mg, 0.68 mmol) in toluene (3 mL) was added 4-chloro-3-(trifluoromethyl)phenyl isocyanate (150 mg, 0.68 mmol). The mixture was stirred at rt for 72 h. The reaction was concentrated under reduced pressure and the residue was triturated with diethylether. The resulting solid was collected by filtration and dried in vacuo for 4 h to afford the title compound (155 mg, 0.32 mmol; 47% yield); 1H-NMR (DMSO-d6) 2.78 (d, J=4.9, 3H), 7.03-7.08 (m, 1H), 7.16 (dd, J=2.6, 5.6, 1H), 7.32 (dd, J=2.7, 11.6, 1H), 7.39 (d, J=2.5, 1H), 7.60 (s, 2H), 8.07-8.18 (m, 2H), 8.50 (d, J=5.7, 1H), 8.72 (s, 1H), 8.74-8.80 (m, 1H), 9.50 (s, 1H); MS (HPLC/ES) 483.06 m/z=(M+1).

後処理

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customthe residue was triturated with diethylether
  3. filtrationThe resulting solid was collected by filtration
  4. customdried in vacuo for 4 h

出典と根拠

ORDレコード
ord-a0df1dc4c8a148b386b384380c4fcb5a
出典データセット
uspto-grants-2014_01
特許番号
US08637553B2

反応ノート

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