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

HRID 1808613Notes

Reaction equation

HRID 1808613 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-1f677a19a2894133ab1e84217bac6796
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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