Methanol → 2-[(4-{2-[(5-Bromopyridin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

HRID 914393Notes

Reaction equation

HRID 914393 reaction equation
[C:1]([O:5][C:6](=[O:27])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][N:21]=2)=O)[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].CO>O1CCCC1>[C:1]([O:5][C:6](=[O:27])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][NH:19][C:20]2[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][N:21]=2)[N:15]=1)([CH3:9])[CH3:8])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 887MethanolHCID 597592352-[(4-{2-[(5-Bromopyridin-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

Product 1

HCID 597590572-[(4-{2-[(5-Bromopyridin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[(4-{2-[(5-Bromopyridin-2-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (12.5 g) obtained in Example 242-1 was dissolved in tetrahydrofuran (20 mL), 1 mol/L-borane/tetrahydrofuran complex (100 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was ice-cooled, and methanol (100 mL) was added dropwise. After warming to room temperature, the mixture was stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, 2-aminoethanol (40 mL) was added, and the mixture was stirred at 70° C. for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=10:1) to give the title compound (5.7 g) as a colorless oil.

Workup

  1. addition1 mol/L-borane/tetrahydrofuran complex (100 mL) was added under ice-
  2. temperaturecooling
  3. temperaturecooled
  4. temperatureAfter warming to room temperature
  5. stirringthe mixture was stirred for 1 hr
  6. concentrationThe reaction mixture was concentrated under reduced pressure, 2-aminoethanol (40 mL)
  7. additionwas added
  8. stirringthe mixture was stirred at 70° C. for 1 hr
  9. additionWater was added to the reaction mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-1374375e8da84aa6b6f1db6682d7c50b
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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