Hydrochloric Acid → (S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide

HRID 1670585Notes

Reaction equation

HRID 1670585 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C[Al](C)C.[Cl:21][C:22]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][CH2:25][N:26]2[C@H:32]1[CH2:36][CH2:35][O:34][C:33]1=[O:37].Cl>ClCCCl>[Cl:21][C:22]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][CH2:25][N:26]2[C@@H:32]([CH2:36][CH2:35][OH:34])[C:33]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([S:8](=[O:9])(=[O:10])[NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[CH:6][N:7]=1)=[O:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 575512216-amino-N-(thiazol-2-yl)pyridine-3-sulfonamideHCID 59465668(S)-3-(4-chloro-5-fluoroindolin-1-yl)dihydrofuran-2(3H)-one

Product 1

HCID 57665817(S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamideYield 26%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

Prepared using General Procedure 2. To a stirring suspension of the 6-amino-N-(thiazol-2-yl)pyridine-3-sulfonamide (92 mg, 0.36 mmol) and DCE (2.0 mL) under N2, at RT, was added 2 M trimethylaluminum in hexanes (0.18 mL, 0.36 mmol) dropwise over 5 minutes. The solution was stirred at ambient temperature for 30 minutes. To this solution was added, a solution of (S)-3-(4-chloro-5-fluoroindolin-1-yl)dihydrofuran-2(3H)-one (92 mg, 0.36 mmol) in DCE (1.0 mL) over 5 minutes. The solution was stirred at 70° C. for 19 hours. The solution was cooled to 0° C. and aqueous 1.0 M HCl was added dropwise. The organic portion was washed with 1.0 N aqueous HCl (2×5.0 mL) and evaporated to dryness under reduced pressure. The residue was purified via silica gel chromatography using 5%-10% MeOH in CH2Cl2 to obtain (S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide (47 mg, 26%) as a yellow solid.

Workup

  1. customPrepared
  2. additionTo this solution was added
  3. stirringThe solution was stirred at 70° C. for 19 hours
  4. temperatureThe solution was cooled to 0° C.
  5. washThe organic portion was washed with 1.0 N aqueous HCl (2×5.0 mL)
  6. customevaporated to dryness under reduced pressure
  7. customThe residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-b1eaa7b1234e47e992ec871aa0f57ca3
Source dataset
uspto-grants-2011_08
Patent number
US07994174B2

Reaction notes

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