Water → 2-({4-[3-(Heptylamino)propyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester

HRID 914442Notes

Reaction equation

HRID 914442 reaction equation
[C:1]([O:5][C:6](=[O:20])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][CH2:18][NH2:19])[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:28](Cl)(=O)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].O>ClCCl>[C:1]([O:5][C:6](=[O:20])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][CH2:18][NH:19][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[N:15]=1)([CH3:9])[CH3:8])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 17313Heptanoyl chlorideHCID 597590072-{[4-(3-Aminopropyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester

Product 1

HCID 597590502-({4-[3-(Heptylamino)propyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-{[4-(3-Aminopropyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester (3.16 g) synthesized in Example 33 and triethylamine (1.68 mL) were dissolved in dichloromethane (50 mL), heptanoyl chloride (1.62 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and 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 dissolved in tetrahydrofuran (10 mL), 1 M-borane/tetrahydrofuran complex (26.6 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 (30 mL) was added dropwise. After warming to room temperature, the mixture was stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, piperidine (30 mL) was added, and the mixture was stirred at 60° C. for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; chloroform:methanol=50:1) to give the title compound (2.86 g) as a colorless oil.

Workup

  1. temperaturecooling
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
  6. addition1 M-borane/tetrahydrofuran complex (26.6 mL) was added under ice-
  7. temperaturecooling
  8. stirringthe mixture was stirred at room temperature for 12 hr
  9. temperaturecooled
  10. additionmethanol (30 mL) was added dropwise
  11. temperatureAfter warming to room temperature
  12. stirringthe mixture was stirred for 1 hr
  13. concentrationThe reaction mixture was concentrated under reduced pressure, piperidine (30 mL)
  14. additionwas added
  15. stirringthe mixture was stirred at 60° C. for 3 hr
  16. concentrationThe reaction mixture was concentrated under reduced pressure
  17. customthe residue was purified by silica gel chromatography (elution solvent; chloroform:methanol=50:1)

Sources & evidence

ORD record
ord-83f6258e952f4cbaa0bfcc243c1b78cf
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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