Hydrochloric Acid → HCID 68950931, compound

HRID 1453842Notes

Reaction equation

HRID 1453842 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:24]([O:26][CH3:27])=[O:25])=[N:11][N:12]2[CH:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:16]NC(=O)[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].IC.Cl.[CH3:33][N:34]([CH:36]=[O:37])[CH3:35]>>[CH2:1]([O:8][C:9]1[C:10]([C:24]([O:26][CH3:27])=[O:25])=[N:11][N:12]2[C:17]([CH3:16])([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:33][N:34]([CH3:35])[C:36](=[O:37])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57528488Methyl 3-benzyloxy-7-ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate

Product 1

HCID 68950931HCID 68950931, compound

Procedure

To a solution of methyl 3-benzyloxy-7-ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate (500 mg, 1.34 mmol) in anhydrous DMF at 0° C. were added sodium hydride (35 mg, 1.47 mmol, 95% dispersion in oil) and iodomethane (100 μL, 1.61 mmol). The reaction was stirred for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous 3N HCl (447 μL, 1.34 mmol) and partitioned between EtOAc and H2O. The aqueous layer was extracted several times with EtOAc, and the combined organic extracts were dried over Na2SO4 and concentrated to a yellow residue. Purification 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 the title product as a clear oil. 1H NMR (400 MHz, d6-DMSO) δ 7.49-7.47 (m, 2H), 7.43-7.31 (m, 3H), 5.20 (dd, J=11.2, 39.6 Hz, 2H), 4.19-4.11 (m, 2H), 3.98 (q, J=13.6 Hz, 2H), 3.80 (s, 3H), 2.99 (s, 3H), 1.81 (s, 3H), 1.13 (t, J=7.2 Hz, 3H); ES MS (M+H)=402.

Workup

  1. custompartitioned between EtOAc and H2O
  2. extractionThe aqueous layer was extracted several times with EtOAc
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. concentrationconcentrated to a yellow residue
  5. customPurification by reverse phase chromatography on a C-18 column
  6. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-9ac149b3f6af4b07b1eb17e538ad4d6f
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

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