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

HRID 1480926Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1480926
[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]

Komponenten

6

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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. Step 2: The title compound was prepared via conversion from its ethyl ester according to general procedure Y: MS (ES) M+Na expected 484.0, found 484.0.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-a8b62bcf567c446a9b90b802ff1409db
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409909B2

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