Hydrochloric Acid → Ethyl 2'-iodo-4'-oxo-5',7'-dihydro-4'H-spiro[cyclopropane-1,6'-pyrazolo[1,5-a]pyrazine]-3'-carboxylate

HRID 920835Notes

Reaction equation

HRID 920835 reaction equation
C(OC([NH:8][C:9]1([CH2:12][N:13]2[C:17]([C:18](OCC)=[O:19])=[C:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:15]([I:28])=[N:14]2)[CH2:11][CH2:10]1)=O)(C)(C)C.Cl>O1CCOCC1>[I:28][C:15]1[C:16]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:17]2[C:18](=[O:19])[NH:8][C:9]3([CH2:11][CH2:10]3)[CH2:12][N:13]2[N:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118062915Diethyl 1-((1-((tert-butoxycarbonyl)amino)cyclopropyl)methyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

Product 1

HCID 118061735Ethyl 2'-iodo-4'-oxo-5',7'-dihydro-4'H-spiro[cyclopropane-1,6'-pyrazolo[1,5-a]pyrazine]-3'-carboxylateYield 73.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of Intermediate 350A (2.1 g, 4.14 mmol) in 1,4-dioxane (10.0 mL) was added 4 M HCl in dioxane (10 mL, 41 mmol) and the resulting solution stirred at RT for 1 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 350B as a pale yellow solid (1.1 g, 60%). MS(ES): m/z=362 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ ppm 6.93 (s, 1H), 4.41 (q, J=7.0 Hz, 2H), 4.26 (s, 2H), 1.41 (t, J=7.0 Hz, 3H), 1.11-0.85 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with EtOAc (50 mL) The organic layer
  3. washwas 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-5a8329a2a3dd4cd9a32c555c8187ea7f
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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