Water → N-{5-hydroxy-2-[5-(thiomorpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl)-N-methylpyridine-2-sulfonamide

HRID 1960410Notes

Reaction equation

HRID 1960410 reaction equation
C([O:7][C:8]1[CH:9]=[C:10]2[C:14](=[C:15]([N:17]([CH3:27])[S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)(=[O:20])=[O:19])[CH:16]=1)[NH:13][C:12]([C:28]1[S:29][CH:30]([CH:33](OC)OC)[CH2:31][N:32]=1)=[CH:11]2)(=O)C(C)(C)C.O.S(=O)(=O)(O)O.C(=O)([O-])O.[Na+].F[C:50](F)(F)[C:51](O)=O>>[OH:7][C:8]1[CH:9]=[C:10]2[C:14](=[C:15]([N:17]([CH3:27])[S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)(=[O:19])=[O:20])[CH:16]=1)[NH:13][C:12]([C:28]1[S:29][CH:30]([CH2:33][N:13]3[CH2:51][CH2:50][S:29][CH2:28][CH2:12]3)[CH2:31][N:32]=1)=[CH:11]2

Participants

6

Reactant 5

HCID 962WaterHCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 59135593HCID 59135593, compound

Product 1

HCID 57476413N-{5-hydroxy-2-[5-(thiomorpholinomethyl)-4,5-dihydro-1,3-thiazol-2-yl]-1H-indol-7-yl)-N-methylpyridine-2-sulfonamideYield 85%

Conditions

Temperature
80 °C

Procedure

To a solution of 2-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indol-5-yl pivalate (273 mg) in trifluoroacetic acid (2 mL) were added water (4 mL) and concentrated sulfuric acid (2 mL), and the mixture was stirred at 80° C. for 5 hr, basified with saturated aqueous sodium hydrogencarbonate, and extracted with ethyl acetate. The organic layer was diluted with ethyl acetate, washed with water and saturated brine, dried (MgSO4), and concentrated under reduced pressure. To a tetrahydrofuran solution (5 mL) of the residue were added thiomorpholine (0.041 mL) and sodium triacetoxyborohydride (215 mg), and the mixture was stirred overnight at room temperature. Saturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the reaction solution, and the organic layer was washed with water and saturated brine, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1-1:2) to give the title compound (145 mg, yield 85%) as a colorless amorphous powder. MS: 504(MH+).

Workup

  1. extractionextracted with ethyl acetate
  2. additionThe organic layer was diluted with ethyl acetate
  3. washwashed with water and saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. additionTo a tetrahydrofuran solution (5 mL) of the residue were added thiomorpholine (0.041 mL) and sodium triacetoxyborohydride (215 mg)
  7. stirringthe mixture was stirred overnight at room temperature
  8. additionSaturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the reaction solution
  9. washthe organic layer was washed with water and saturated brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1-1:2)

Sources & evidence

ORD record
ord-be6ac72b57304848a3226b8c879176c8
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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