Potassium Iodide → 5-Benzyl-2-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 920707Notes

Reaction equation

HRID 920707 reaction equation
Br[CH2:2][CH2:3][N:4]1[C:8]([C:9]([O:11]CC)=O)=[CH:7][C:6]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[N:5]1.[I-].[K+].[CH2:23]([NH2:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(#N)C>[CH2:23]([N:30]1[CH2:2][CH2:3][N:4]2[N:5]=[C:6]([C:14]3[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=3)[CH:7]=[C:8]2[C:9]1=[O:11])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 7504BenzylamineHCID 118061974Ethyl 1-(2-bromoethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxylate

Product 1

HCID 1180612625-Benzyl-2-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-oneYield 46.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of Intermediate 1C (80 g, 234 mmol) and potassium iodide (78 g, 469 mmol) in acetonitrile (800 mL) was added benzyl amine (28.2 mL, 258 mmol) and the reaction mixture was stirred at 90° C. for 12 h. Acetonitrile was removed under reduced pressure, crude was diluted with water and the aqueous layer was extracted with DCM (3×500 mL). The combined organic layer washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (120 g REDISEP® column, eluting with 1-2% methanol in chloroform). Collected fractions were concentrated together to afford Intermediate 1D (35 g, 46%). MS(ES): m/z=322 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 7.71-7.83 (m, 2H), 7.29-7.42 (m, 5H), 7.14 (s, 1H), 7.06-7.12 (m, 2H), 4.78 (s, 2H), 4.32-4.40 (m, 2H), 3.63-3.75 (m, 2H).

Workup

  1. customAcetonitrile was removed under reduced pressure, crude
  2. additionwas diluted with water
  3. extractionthe aqueous layer was extracted with DCM (3×500 mL)
  4. washThe combined organic layer washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (120 g REDISEP® column, eluting with 1-2% methanol in chloroform)
  9. concentrationCollected fractions were concentrated together

Sources & evidence

ORD record
ord-541df58aeb604e068c50f8c78be44b42
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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