Hydrochloric Acid → Ethyl 2-iodo-6-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylate

HRID 920817Notes

Reaction equation

HRID 920817 reaction equation
C(OC([NH:8][CH:9]([CH3:27])[CH2:10][N:11]1[C:15]([C:16](OCC)=[O:17])=[C:14]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:13]([I:26])=[N:12]1)=O)(C)(C)C.Cl>O1CCOCC1>[I:26][C:13]1[C:14]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:15]2[C:16](=[O:17])[NH:8][CH:9]([CH3:27])[CH2:10][N:11]2[N:12]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118061851Diethyl 1-(2-((tert-butoxycarbonyl)amino)propyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

Product 1

HCID 118062510Ethyl 2-iodo-6-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of Intermediate 340A (7.0 g, 14.13 mmol) in 1,4-dioxane (10 mL) was added 4 M HCl in dioxane (25 mL, 100 mmol) and the solution was stirred at RT for 2 h. The reaction mixture was concentrated and the residue was diluted with EtOAc (20 mL). The EtOAc solution was washed successively with water, a saturated aq. solution of NaHCO3, and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue obtained was heated in a ROTAVAPOR® at 60° C. for 5 h. The solid product was washed with ether to afford Intermediate 340B (4.0 g, 87%). MS(ES): m/z=350 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.49 (s, 1H), 4.27-4.49 (m, 1H), 4.11-4.26 (m, 2H), 4.03 (d, J=11.71 Hz, 2H), 1.06-1.39 (m, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with EtOAc (20 mL)
  3. washThe EtOAc solution was washed successively with water
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. temperaturewas heated in a ROTAVAPOR® at 60° C. for 5 h
  9. washThe solid product was washed with ether

Sources & evidence

ORD record
ord-0f34e7931e7b498d92b44b2088fa658f
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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