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

HRID 459644

Reaktionsgleichung

Reaktionsgleichung von HRID 459644
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[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.[CH3:45][N:46]1[C:50]([NH2:51])=[C:49]([NH2:52])[CH:48]=[N:47]1>O1CCCC1.O.C(Cl)(Cl)Cl>[NH2:51][C:50]1[N:46]([CH3:45])[N:47]=[CH:48][C:49]=1[NH:52][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][CH2:19][NH:20][C:21](=[O:22])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:15]

Komponenten

8

Edukt 4

HCID 6586Methyl chloroformateHCID 8471Triethylamine2×HCID 98765IN2-(benzyloxycarbonyl)-N6-(tert-butoxycarbonyl)-L-lysineHCID 219045711H-Pyrazole, 4,5-diamine-1-methyl-, sulfate (1:1)

Produkt 1

HCID 865978971-benzyl 5-tert-butyl (1S)-{1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]pentamethylene}biscarbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6212ChloroformLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (2S)-2-[(benzyloxycarbonyl)amino]-6-[(tert-butoxycarbonyl)amino]hexanoic acid (19.02 g) and triethylamine (5.56 g) in tetrahydrofuran (200 ml) was added methyl chloroformate (4.21 ml), 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 (15.75 g) and triethylamine (15.2 g) in water (50 ml) at the same temperature. The mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added chloroform (300 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 5-tert-butyl (1S)-{1-[(5-amino-1-methyl-1H-pyrazol-4-yl)carbamoyl]pentamethylene}biscarbamate as an oil. The crude product was used directly in the next step without further purification.

Aufarbeitung

  1. temperaturecooling for 30 minutes
  2. stirringThe mixture was stirred at room temperature for 30 minutes
  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

Quellen und Nachweise

ORD-Eintrag
ord-c0874084eb7f46c7bf88e13c69e218d5
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07192943B2

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