Boron tribromide → 3-[(3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-7-fluoro-4-hydroxy-1H-indazol-1-yl)methyl]benzamide

HRID 1874719ノート

反応式

HRID 1874719 の反応式
[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[C:15]([F:22])[CH:16]=[CH:17][C:18]=3[O:20]C)[N:13]([CH2:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([NH2:29])=[O:28])[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[C:19]3[C:14](=[C:15]([F:22])[CH:16]=[CH:17][C:18]=3[OH:20])[N:13]([CH2:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([NH2:29])=[O:28])[N:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 594560953-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide

生成物 1

HCID 1361160273-[(3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-7-fluoro-4-hydroxy-1H-indazol-1-yl)methyl]benzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A suspension of 3-{[3-{[(5-chloro-2-thienyl)sulfonyl]amino}-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide (for a preparation see Example 68) (15.7 mg, 0.032 mmol) in anhydrous DCM (2 mL) under nitrogen atmosphere was treated with boron tribromide solution in DCM (1M, 0.032 mL) at room temperature. The reaction mixture was stirred at room temperature for 45 min and then saturated aqueous sodium bicarbonate solution was added dropwise to quench the reaction. The mixture was then partitioned between further saturated aqueous sodium bicarbonate solution and 10% methanol in ethyl acetate (white precipitate was present which was insoluble in both the organic and aqueous layer). The organic layer was separated, passed through an hydrophobic frit and evaporated in-vacuo to yield a yellow solid (13 mg). This was dissolved in MeOH:DMSO (1:1) (0.5 mL) and purified by MDAP on Sunfire C18 column, eluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B: 0.1% v/v solution of formic acid in acetonitrile). Appropriate fraction was evaporated in-vacuo to yield the title compound as a yellow solid (8.5 mg, 56%). LCMS (System B) RT=2.41 min, ES+ve m/z 481/483 (M+H)+.

後処理

  1. customto quench
  2. customthe reaction
  3. customThe mixture was then partitioned between further saturated aqueous sodium bicarbonate solution and 10% methanol in ethyl acetate (white precipitate
  4. customThe organic layer was separated
  5. customevaporated in-vacuo

出典と根拠

ORDレコード
ord-0107c09b1692458da2bba7dd497d88fd
出典データセット
uspto-grants-2012_11
特許番号
US08304446B2

反応ノート

読み込み中…