Methyl chloroformate → 1-benzyl 4-tert-butyl ((1S)-1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]tetramethylene}biscarbamate

HRID 459639

Reaction equation

HRID 459639 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OC)=O.S(O)(O)(=O)=O.[CH3:44][N:45]1[C:49]([NH2:50])=[C:48]([NH2:51])[CH:47]=[N:46]1>O1CCCC1.O.C(Cl)(Cl)Cl>[NH2:50][C:49]1[N:45]([CH3:44])[N:46]=[CH:47][C:48]=1[NH:51][C:13]([C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:21])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:15]

Participants

8

Reactant 4

HCID 6586Methyl chloroformateHCID 8471Triethylamine2×HCID 7350734Z-Ndelta-Boc-L-ornithineHCID 219045711H-Pyrazole, 4,5-diamine-1-methyl-, sulfate (1:1)

Product 1

HCID 865978881-benzyl 4-tert-butyl ((1S)-1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]tetramethylene}biscarbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S)-2-[(benzyloxycarbonyl)amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid (22.0 g) and triethylamine (6.7 g) in tetrahydrofuran (240 ml) was added methyl chloroformate (6.2 g) followed by stirring under ice-cooling for 30 minutes. To the reaction mixture was added a solution of 1-methyl-1H-pyrazole-4,5-diamine sulfate (12.6 g) and triethylamine (13.4 g) in water (50 ml) at the same temperature. The mixture was stirred at the room temperature for 1 hour. To the reaction mixture was added chloroform (240 ml), and the layers were separated. The organic layer was washed successively with 10% aqueous citric acid solution, brine and saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give a crude product of 1-benzyl 4-tert-butyl {(1S)-1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]tetramethylene}biscarbamate as an oil. The crude product was used directly in the next step without further purification.

Workup

  1. temperaturecooling for 30 minutes
  2. stirringThe mixture was stirred at the room temperature for 1 hour
  3. customthe layers were separated
  4. washThe organic layer was washed successively with 10% aqueous citric acid solution, brine and saturated aqueous sodium hydrogencarbonate solution
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9c9e5880ba7c4d1c8e708dfff936c1dc
Source dataset
uspto-grants-2007_03
Patent number
US07192943B2

Linked notes

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