4-Methylmorpholine → N2-[1-benzyl-2-(1-[(1,2-dimethylhydrazino) carbonyl]-3-methylbutylamino)-2-oxoethyl]-2-pyrazinecarboxamide

HRID 339487

Reaction equation

HRID 339487 reaction equation
[CH3:1][CH:2]([CH3:28])[CH2:3][CH:4]([NH:8][C:9](=[O:27])[CH:10]([NH:18][C:19]([C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1)=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([OH:7])=O.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[CH3:45][NH:46][NH:47][CH3:48]>C1COCC1.[OH-].[Na+]>[CH2:11]([CH:10]([NH:18][C:19]([C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1)=[O:20])[C:9]([NH:8][CH:4]([C:5]([N:46]([CH3:45])[NH:47][CH3:48])=[O:7])[CH2:3][CH:2]([CH3:28])[CH3:1])=[O:27])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1344141,2-Dimethylhydrazine hydrochlorideHCID 672089154-Methyl-2-(3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propanoylamino) pentanoic acid

Product 1

HCID 67326475N2-[1-benzyl-2-(1-[(1,2-dimethylhydrazino) carbonyl]-3-methylbutylamino)-2-oxoethyl]-2-pyrazinecarboxamideYield 89%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
-10 °C

Procedure

4-Methyl-2-(3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propanoylamino) pentanoic acid (200 mg, 0.52 mmol) was dissolved in THF (1.2 mL). N-Methylmorpholine (0.057 mL, 0.52 mmol) was added, and the resulting clear solution was cooled to −10° C. Isobutyl chloroformate (0.068 mL, 0.52 mmol) was added dropwise to cause N-Methylmorpholine HCl salt precipitation. N,N′-dimethylhydrazine hydrochloride salt (346 mg, 2.6 mmol) was dissolved in 3N NaOH (1.7 mL). The resulting mixture was added to the solution and stirred for 1 h. The solution was extracted by EtOAc, and washed with 5% NaHSO3, saturated sodium bicarbonate solution, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated by rotary evaporation. Purification by chromatography (silica, 20/1: DCM/MeOH, Rf=0.3) afforded N2-[1-benzyl-2-(1-[(1,2-dimethylhydrazino) carbonyl]-3-methylbutylamino)-2-oxoethyl]-2-pyrazinecarboxamide as a pale yellow solid (197 mg, 89%).

Workup

  1. customN-Methylmorpholine HCl salt precipitation
  2. additionThe resulting mixture was added to the solution
  3. extractionThe solution was extracted by EtOAc
  4. washwashed with 5% NaHSO3, saturated sodium bicarbonate solution, and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customPurification by chromatography (silica, 20/1: DCM/MeOH, Rf=0.3)

Sources & evidence

ORD record
ord-c15b91bbd13d4ed8b93d7035f68c50de
Source dataset
uspto-grants-2014_11
Patent number
US08895497B2

Linked notes

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