Methanol → n-(1-{[3-(Aminomethyl)phenyl]methyl}-4-hydroxy-1h-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt

HRID 1808556ノート

反応式

HRID 1808556 の反応式
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[C:15]([O:20]C)[CH:16]=[CH:17][CH:18]=3)[C:13]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:12]2)[CH:7]=[CH:8][CH:9]=1.B(Br)(Br)Br.CO.[C:38](=O)([OH:40])[O-:39].[Na+]>C(Cl)Cl>[CH:38]([OH:40])=[O:39].[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[C:15]([OH:20])[CH:16]=[CH:17][CH:18]=3)[C:13]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:12]2)[CH:7]=[CH:8][CH:9]=1

参加物

6

反応物 4

HCID 887MethanolHCID 25134Boron tribromide2 回HCID 516892Sodium BicarbonateHCID 66632476HCID 66632476、化合物

生成物 1

HCID 136346357n-(1-{[3-(Aminomethyl)phenyl]methyl}-4-hydroxy-1h-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (266 mg, 0.533 mmol) in anhydrous DCM (7.5 mL) under nitrogen atmosphere was treated dropwise with boron tribromide solution in DCM (1M, 0.533 mL, 0.533 mmol) at room temperature, and the reaction mixture was stirred at room temperature for 1 hour (reaction not in solution—sticky orange gum had formed). A further portion of boron tribromide (1M, 0.533 mL) was added and the reaction mixture was stirred at room temperature for 1 hour (reaction still not in solution). Anhydrous methanol was added dropwise until the reaction was in solution. Reaction mixture was then stirred at room temperature for a further 30 min. Saturated aqueous sodium bicarbonate solution (10 mL) was added dropwise with care to quench the reaction, on addition of which both a white precipitate (suspended in the aqueous layer) and a dark green sticky gum (stuck to the side of the flask) formed. The aqueous and organic layers were applied to a hydrophobic frit and the organic layer collected and retained. The remaining green gum in the flask was dissolved in 1:1 methanol-dichloromethane, passed through a hydrophobic frit, combined with the retained organic and evaporated in-vacuo to yield a dark green sticky solid (265 mg). This was dissolved in DMSO (3×1 mL) and purified by MDAP 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) (25 min run). Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a colourless oil (86 mg, 33%). LCMS (System B) RT=1.63 min, ES+ve m/z 449/451 (M+H)+.

後処理

  1. customreaction not in solution—sticky orange gum
  2. customhad formed)
  3. stirringthe reaction mixture was stirred at room temperature for 1 hour (
  4. customreaction still not in solution)
  5. customReaction mixture
  6. stirringwas then stirred at room temperature for a further 30 min
  7. customto quench
  8. customthe reaction
  9. additionon addition of which both a white precipitate (
  10. customformed
  11. customthe organic layer collected
  12. dissolutionThe remaining green gum in the flask was dissolved in 1:1 methanol-dichloromethane
  13. customevaporated in-vacuo

出典と根拠

ORDレコード
ord-cbcf74dc33f24bd19bcee2cc133e443a
出典データセット
uspto-grants-2013_01
特許番号
US08357716B2

反応ノート

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