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

HRID 920836Notes

Reaction equation

HRID 920836 reaction equation
[I:1][C:2]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[C:6](=O)[NH:7][C:8]3([CH2:11][CH2:10]3)[CH2:9][N:4]2[N:3]=1.CSC>C1COCC1>[I:1][C:2]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[CH2:6][NH:7][C:8]3([CH2:11][CH2:10]3)[CH2:9][N:4]2[N:3]=1

Participants

4

Reactant 2

HCID 1068Dimethyl SulfideHCID 118061735Ethyl 2'-iodo-4'-oxo-5',7'-dihydro-4'H-spiro[cyclopropane-1,6'-pyrazolo[1,5-a]pyrazine]-3'-carboxylate

Product 1

HCID 118061634Ethyl 2'-iodo-5',7'-dihydro-4'H-spiro[cyclopropane-1,6'-pyrazolo[1,5-a]pyrazine]-3'-carboxylateYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 350B (1.1 g, 3.05 mmol) in THF (10 mL) was added BH3.DMS (0.578 mL, 6.09 mmol, 2M) and the resulting solution was stirred at 40° C. for 18 h. The reaction mixture was cooled to RT, quenched with ethanol (10 mL) and heated to reflux for 1 h. Reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 2% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 350C (0.7 g, 66%) as a gummy solid. MS(ES): m/z=348 [M+H]+.

Workup

  1. customquenched with ethanol (10 mL)
  2. temperatureheated
  3. temperatureto reflux for 1 h
  4. customReaction mixture
  5. concentrationwas concentrated under reduced pressure
  6. customThe crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 2% MeOH in CHCl3)
  7. additionFractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-e2c6ac56ffaa4f93b711b83475eb9995
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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