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

HRID 920828Notes

Reaction equation

HRID 920828 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([I:29])=[N:8][N:9]([CH2:16][CH:17]([NH:21][C:22](OC(C)(C)C)=[O:23])[CH:18]2[CH2:20][CH2:19]2)[C:10]=1C(OCC)=O)=[O:5])[CH3:2].Cl>O1CCOCC1>[CH:18]1([CH:17]2[CH2:16][N:9]3[N:8]=[C:7]([I:29])[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[C:10]3[C:22](=[O:23])[NH:21]2)[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118062403Diethyl1-(2-((tert-butoxycarbonyl)amino)-2-cyclopropylethyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

Product 1

HCID 118061773Ethyl 6-cyclopropyl-2-iodo-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of Intermediate 348B (8.0 g, 15.34 mmol) in 1,4-dioxane (10.0 mL) was added 4 M HCl in dioxane (40.0 mL, 160 mmol) and the resulting solution stirred at RT for 2 h. The reaction mixture was concentrated and diluted with EtOAc (50 mL). The organic layer was washed successively with water, a saturated aq. solution of NaHCO3, and brine, then dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The residue obtained was heated in a ROTAVAPOR® at 60° C. for 5 h. The solid product was triturated with diethyl ether to afford Intermediate 348C as an off-white solid (1.6 g, 28%). MS(ES): m/z=376 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.67 (d, J=2.27 Hz, 1H), 4.47 (dd, J=13.22, 4.53 Hz, 1H), 4.17-4.33 (m, 3H), 3.15 (d, J=9.07 Hz, 1H), 1.28 (s, 3H), 0.90 (d, J=8.69 Hz, 1H), 0.40-0.54 (m, 2H), 0.20-0.37 (m, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with EtOAc (50 mL)
  3. washThe organic layer was washed successively with water
  4. dry with materiala saturated aq. solution of NaHCO3, and brine, then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue obtained
  8. temperaturewas heated in a ROTAVAPOR® at 60° C. for 5 h
  9. customThe solid product was triturated with diethyl ether

Sources & evidence

ORD record
ord-931aebb6ed9c44b99e7c1c51dfd3517c
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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