Ammonia → Methyl 3-benzyloxy-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

HRID 1453826Notes

Reaction equation

HRID 1453826 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:27]([O:29][CH3:30])=[O:28])=[N:11][N:12]([CH:18]([C:25]#[N:26])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]=1[C:14]([O:16]C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N>CO.[Rh]>[CH2:1]([O:8][C:9]1[C:10]([C:27]([O:29][CH3:30])=[O:28])=[N:11][N:12]2[CH:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:25][NH:26][C:14](=[O:16])[C:13]=12)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 222AmmoniaHCID 68953781Dimethyl 4-benzyloxy-1-[cyano(phenyl)methyl]-1H-pyrazole-3,5-dicarboxylate

Product 1

HCID 68951327Methyl 3-benzyloxy-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of dimethyl 4-benzyloxy-1-[cyano(phenyl)methyl]-1H-pyrazole-3,5-dicarboxylate (1.0 g, 2.47 mmol) in anhydrous MeOH (100 mL) through which nitrogen had been bubbled was added rhodium on alumina (50 mg). The mixture was then treated with ammonia gas for 5 minutes and stirred under an atmosphere of hydrogen gas overnight. The mixture was filtered through celite and the filter cake was washed with MeOH. The filtrate was concentrated and purified by reverse phase chromatography on a C-18 column using a gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA). Collection and concentration of the appropriate fractions afforded the title product as an off-white solid. 1H NMR (400 MHz, d6-DMSO) δ 8.28 (s, 1H), 7.49-7.47 (m, 2H), 7.40-7.32 (m, 6H), 6.96-6.93 (m, 2H), 5.77 (s, 1H), 5.40-5.27 (m, 2H), 4.04-3.99 (m, 1H), 3.78 (s, 3H), 3.76-3.59 (m, 1H); ES MS (M+1)=378.

Workup

  1. filtrationThe mixture was filtered through celite
  2. washthe filter cake was washed with MeOH
  3. concentrationThe filtrate was concentrated
  4. custompurified by reverse phase chromatography on a C-18 column
  5. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA)
  6. customCollection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-53d4f8fa030a4266baab990f5f53eead
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

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