Trifluoroacetic acid → Methyl 3-benzyloxy-7-ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

HRID 1453838Notes

Reaction equation

HRID 1453838 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:33]([O:35][CH3:36])=[O:34])=[N:11][N:12]([CH:18]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:19][NH:20][C:21]([O:23]C(C)(C)C)=O)[C:13]=1C(OC)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl.CCOC(C)=O>[CH2:1]([O:8][C:9]1[C:10]([C:33]([O:35][CH3:36])=[O:34])=[N:11][N:12]2[CH:18]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:19][NH:20][C:21](=[O:23])[C:13]=12)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68952340Dimethyl 4-benzyloxy-1-{2-[(tert-butoxycarbonyl)amino]-1-(ethoxycarbonyl)ethyl}-1H-pyrazole-3,5-dicarboxylate

Product 1

HCID 57528488Methyl 3-benzyloxy-7-ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of dimethyl 4-(benzyloxy)-1-{2-[(tert-butoxycarbonyl)amino]-1-(ethoxycarbonyl)ethyl}-1H-pyrazole-3,5-dicarboxylate (6.97 g, 13.78 mmol) in CHCl3 (150 mL) was added TFA (30 mL). The reaction was allowed to stir at room temperature overnight. The solvent was removed in vacuo, and the residue was partitioned between saturated aqueous NaHCO3 solution and CHCl3. The aqueous layer was extracted three times with CHCl3, and the combined organic extracts were dried over Na2SO4. Concentration in vacuo afforded a yellow oil which was dissolved in EtOAc (30 mL) and sonicated. The resulting precipitate was collected by filtration to afford the title product as a white solid. The filtrate was further 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), and collection and concentration of the appropriate fractions afforded additional title product as a white solid. 1H NMR (400 MHz, d6-DMSO) δ 8.38 (d, J=5.2 Hz, 1H), 6.45-7.43 (m, 2H), 7.38-7.30 (m, 3H), 5.55 (d, J=4.0 Hz, 1H), 5.26 (dd, J=11.2, 40.0 Hz, 2H), 4.23-4.14 (m, 2H), 3.97 (dd, J=5.0, 13.8 Hz, 1H), 3.79 (s, 3H), 3.71 (dd, J=5.4, 13.8 Hz, 1H), 1.18 (t, J=7.0 Hz, 3H); ES MS (M+H)=374.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between saturated aqueous NaHCO3 solution and CHCl3
  3. extractionThe aqueous layer was extracted three times with CHCl3
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. concentrationConcentration in vacuo
  6. customafforded a yellow oil which
  7. customsonicated
  8. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-0d63fcd47efe4e4ea4e052cb46303714
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

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