Methanol → 2-methyl-2-{[4-(2-{[(1-phenyl-1H-pyrazol-4-yl)methyl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester

HRID 914380Notes

Reaction equation

HRID 914380 reaction equation
[C:1]([O:5][C:6](=[O:32])[C:7]([CH3:31])([S:9][C:10]1[S:11][CH:12]=[C:13]([CH2:15][CH2:16][NH:17][C:18]([C:20]2[CH:21]=[N:22][N:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:24]=2)=O)[N:14]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].CO>O1CCCC1>[C:1]([O:5][C:6](=[O:32])[C:7]([CH3:8])([S:9][C:10]1[S:11][CH:12]=[C:13]([CH2:15][CH2:16][NH:17][CH2:18][C:20]2[CH:21]=[N:22][N:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:24]=2)[N:14]=1)[CH3:31])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 887MethanolHCID 597589112-methyl-2-{[4-(2-{[(1-phenyl-1H-pyrazol-4-yl)carbonyl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester

Product 1

HCID 597588602-methyl-2-{[4-(2-{[(1-phenyl-1H-pyrazol-4-yl)methyl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl esterYield 60.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Methyl-2-{[4-(2-{[(1-phenyl-1H-pyrazol-4-yl)carbonyl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester (16.2 g) obtained in Example 451-1 was dissolved in tetrahydrofuran (20 mL), 1 mol/L-borane/tetrahydrofuran complex (160 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 (200 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 (60 mL) was added, and the mixture was stirred at 60° C. for 4 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; dichloromethane:methanol=20:1 to 10:1) to give the title compound (9.5 g) as a slightly yellow oil.

Workup

  1. addition1 mol/L-borane/tetrahydrofuran complex (160 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, piperidine (60 mL)
  7. additionwas added
  8. stirringthe mixture was stirred at 60° C. for 4 hr
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. customthe residue was purified by silica gel chromatography (elution solvent; dichloromethane:methanol=20:1 to 10:1)

Sources & evidence

ORD record
ord-c8fd70a327ac43d2b7a83c7c601724bd
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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