Cesium carbonate → 2[(2-fluorobenzyl)oxy]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1396509Notes

Reaction equation

HRID 1396509 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[F:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]3[N:23]=[C:24]([OH:26])[CH:25]=[C:19]3[C:18]2=[O:27])=[CH:13][CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][O:26][C:24]1[CH:25]=[C:19]2[C:18](=[O:27])[N:17]([C:14]3[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=3)[CH2:22][CH2:21][N:20]2[N:23]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 67968alpha-Bromo-o-fluorotolueneHCID 178515148HCID 178515148, compound

Product 1

HCID 727147862[(2-fluorobenzyl)oxy]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-oneYield 85.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Fluorobenzyl bromide (0.049 mL, 0.39 mmol) was added to a stirred suspension of 5-(4-fluorophenyl)-2-hydroxy-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.092 g, 0.36 mmol) and Cs2CO3 (0.234 g, 0.72 mmol) in ACN (1.85 mL). The mixture was stirred at room temperature for 16 hours. The solvent was evaporated in vacuo. The residue was diluted with water and extracted with AcOEt. The organic layer was separated, washed with a saturated solution of NaCl, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in heptane 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield 2[(2-fluorobenzyl)oxy]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (0.109 g, 85% yield) as a white solid. C19H15F2N3O2. 1H NMR (500 MHz, CDCl3) δ ppm 4.14 (dd, J=6.8, 5.1 Hz, 2H), 4.37 (dd, J=6.9, 5.2 Hz, 2H), 5.30 (s, 2H), 6.37 (s, 1H), 7.04-7.15 (m, 3H), 7.17 (td, J=7.5, 0.9 Hz, 1H), 7.28-7.36 (m, 3H), 7.53 (td, J=7.4, 1.4 Hz, 1H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. additionThe residue was diluted with water
  3. extractionextracted with AcOEt
  4. customThe organic layer was separated
  5. washwashed with a saturated solution of NaCl
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvents evaporated in vacuo
  9. customThe crude product was purified by flash column chromatography (silica; AcOEt in heptane 0/100 to 50/50)
  10. customThe desired fractions were collected
  11. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-30417d5a5e404cd4812ecd1a025d1f39
Source dataset
uspto-grants-2014_12
Patent number
US08901125B2

Reaction notes

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