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

HRID 1892953Notes

Reaction equation

HRID 1892953 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[C:6]([F:13])[CH:7]=[CH:8][C:9]=2[O:11][CH3:12])[N:4]([CH2:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18]([NH2:20])=[O:19])[N:3]=1.[Cl:24][C:25]1[S:29][C:28]([S:30](Cl)(=[O:32])=[O:31])=[CH:27][CH:26]=1>N1C=CC=CC=1.ClCCl.CO.CS(C)=O>[Cl:24][C:25]1[S:29][C:28]([S:30]([NH:1][C:2]2[C:10]3[C:5](=[C:6]([F:13])[CH:7]=[CH:8][C:9]=3[O:11][CH3:12])[N:4]([CH2:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([NH2:20])=[O:19])[N:3]=2)(=[O:32])=[O:31])=[CH:27][CH:26]=1

Participants

6

Reactant 2

HCID 27339255-Chlorothiophene-2-sulfonyl chloride2×HCID 580545553-{[3-amino-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide

Product 1

HCID 594560953-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamideYield 45%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×HCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To a solution of 3-{[3-amino-7-fluoro-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide (for a preparation see Intermediate 14) (22 mg, 0.07 mmol) in anhydrous pyridine (1 mL) and anhydrous dichloromethane (3 mL) (gentle heating of the mixture for a few minutes with a heatgun was required in order for the starting material to go in solution) was added a solution of 5-chloro-2-thiophenesulfonyl chloride (16.71 mg, 0.077 mmol) in anhydrous dichloromethane (0.5 mL). The reaction was stirred at room temperature for 45 min, then at 45° C. for 30 min. A solution of 5-chloro-2-thiophenesulfonyl chloride (16.7 mg) in anhydrous dichloromethane (0.2 mL) was added to the reaction mixture and stirred at 45° C. for 25 h. The reaction mixture was cooled and then partitioned between water and dichloromethane. The organic layer was passed through an hydrophobic frit and evaporated in-vacuo to yield a pale yellow solid. The solid was dissolved in MeOH-DMSO (1 mL) and purified by MDAP on Sunfire C18 column, eluting with solvents NB (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 white solid (15.7 mg, 45%). LCMS (5 min run) RT=2.62 min, ES+ve m/z 495/497 (M+H)+.

Workup

  1. waitat 45° C. for 30 min
  2. stirringstirred at 45° C. for 25 h
  3. temperatureThe reaction mixture was cooled
  4. custompartitioned between water and dichloromethane
  5. customevaporated in-vacuo
  6. customto yield a pale yellow solid
  7. custompurified by MDAP on Sunfire C18 column
  8. washeluting with solvents NB (A: 0.1% v/v solution of formic acid in water, B
  9. customAppropriate fraction was evaporated in-vacuo

Sources & evidence

ORD record
ord-2ec1363fee7342f38a984a7b2772d101
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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