Methanesulfonyl chloride → 4-(4-Chloro-2-[1,2,3]triazolo[4,5-b]pyridin-1-yl-phenylsulfamoyl)-2-fluoro-benzoic acid ethyl ester

HRID 218219Notes

Reaction equation

HRID 218219 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([N:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[N:10]2)[CH:3]=1.[CH2:18]([O:20][C:21](=[O:33])[C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][C:23]=1[F:32])[CH3:19].CS(Cl)(=O)=O>N1C=CC=CC=1.CCOC(C)=O>[CH2:18]([O:20][C:21](=[O:33])[C:22]1[CH:27]=[CH:26][C:25]([S:28](=[O:29])(=[O:30])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[N:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[N:10]2)=[CH:24][C:23]=1[F:32])[CH3:19]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 594281144-Chloro-2-[1,2,3]triazolo[4,5-b]pyridin-1-yl-phenylamineHCID 594281294-Chlorosulfonyl-2-fluoro-benzoic acid ethyl ester

Product 1

HCID 594281364-(4-Chloro-2-[1,2,3]triazolo[4,5-b]pyridin-1-yl-phenylsulfamoyl)-2-fluoro-benzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-chloro-2-[1,2,3]triazolo[4,5-b]pyridin-1-yl-phenylamine (153.5 mg, 0.626 mmol) in pyridine (2 mL) was added 4-chlorosulfonyl-2-fluoro-benzoic acid ethyl ester (200 mg, 0.752 mmol) followed by methanesulfonyl chloride (32 μL, 0.47 mmol) at 0° C. under a nitrogen atmosphere. The resultant reaction mixture was allowed to warm to room temperature and stirred for overnight. The following day, reaction mixture was diluted with EtOAc (25 mL), washed with 2N HCl (2×15 mL), dried (Na2SO4) and evaporated. The resulting bis-sulfonamides crude mixture was treated with 1N TBAF (in THF, 2 mL) at room temperature for 1 hour. The reaction mixture was then diluted with EtOAc (25 mL), washed with 2 N HCl (2×15 mL), water (10 mL), brine (10 mL), dried (Na2SO4) and evaporated. The resulting crude product was purified by SiO2 chromatography using 50→100% EtOAc in hexanes solvent system to obtain 4-(4-chloro-2-[1,2,3]triazolo[4,5-b]pyridin-1-yl-phenylsulfamoyl)-2-fluoro-benzoic acid ethyl ester.

Workup

  1. customThe resultant reaction mixture
  2. customThe following day, reaction mixture
  3. washwashed with 2N HCl (2×15 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. additionThe resulting bis-sulfonamides crude mixture was treated with 1N TBAF (in THF, 2 mL) at room temperature for 1 hour
  7. additionThe reaction mixture was then diluted with EtOAc (25 mL)
  8. washwashed with 2 N HCl (2×15 mL), water (10 mL), brine (10 mL)
  9. dry with materialdried (Na2SO4)
  10. customevaporated
  11. customThe resulting crude product was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-dcac8ebfd6c241bb8abc47fdcd4a2597
Source dataset
uspto-grants-2012_06
Patent number
US08198309B2

Reaction notes

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