Sodium Chloride → tert-butyl {(3S)-4-[(5-amino-1-methyl-1H-pyrazol-4-yl)amino]-3-hydroxy-4-oxobutyl)carbamate

HRID 1247811Notes

Reaction equation

HRID 1247811 reaction equation
S(O)(O)(=O)=O.[CH3:6][N:7]1[C:11]([NH2:12])=[C:10]([NH2:13])[CH:9]=[N:8]1.[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][C@H:24]([OH:28])[C:25](O)=[O:26])=[O:20])([CH3:17])([CH3:16])[CH3:15].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+].[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[NH2:12][C:11]1[N:7]([CH3:6])[N:8]=[CH:9][C:10]=1[NH:13][C:25](=[O:26])[C@@H:24]([OH:28])[CH2:23][CH2:22][NH:21][C:19](=[O:20])[O:18][C:14]([CH3:15])([CH3:16])[CH3:17]

Participants

10

Reactant 6

HCID 5234Sodium ChlorideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11816837(2S)-4-(((tert-butoxy)carbonyl)amino)-2-hydroxybutanoic acidHCID 219045711H-Pyrazole, 4,5-diamine-1-methyl-, sulfate (1:1)

Product 1

HCID 86593406tert-butyl {(3S)-4-[(5-amino-1-methyl-1H-pyrazol-4-yl)amino]-3-hydroxy-4-oxobutyl)carbamateYield 58.9%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 1-methyl-1H-pyrazole-4,5-diamine sulfate (86 g) in tetrahydrofuran (1.3 L) was added triethylamine (117 ml), and then (2S)-4-[(tert-butoxycarbonyl)amino]-2-hydroxybutanoic acid (82.5 g) was added to the mixture. To the mixture were added 1-hydroxybenzotriazole (58.3 g) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (82.7 g) under ice-cooling. The reaction mixture was stirred at room temperature for 8 hours. To the reaction mixture were added ethyl acetate (1.3 L), saturated aqueous sodium hydrogen carbonate solution and sodium chloride, and the mixture was stirred for 30 minutes. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (1.0 L) six times. The extract was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with ethyl acetate/tetrahydrofuran (1/1) to give tert-butyl {(3S)-4-[(5-amino-1-methyl-1H-pyrazol-4-yl)amino]-3-hydroxy-4-oxobutyl}carbamate (69.5 g).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 30 minutes
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (1.0 L) six times
  5. dry with materialThe extract was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with ethyl acetate/tetrahydrofuran (1/1)

Sources & evidence

ORD record
ord-d173e63b27594994b101f3cde68dcabb
Source dataset
uspto-grants-2006_10
Patent number
US07129232B2

Reaction notes

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