1-Bromo-4-fluorobenzene → 2-(benzyloxy)-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1396506Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:18]=[C:12]2[C:13](=[O:17])[NH:14][CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1.CN(C)CCN.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[CH2:1]([O:8][C:9]1[CH:18]=[C:12]2[C:13](=[O:17])[N:14]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH2:15][CH2:16][N:11]2[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 140 °C

Procedure

Copper (I) iodide (0.74 g, 3.88 mmol) was added to a stirred suspension of 2-(benzyloxy)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (1.5 g, 6.17 mmol), 4-bromofluorobenzene (2.03 mL, 18.5 mmol), N,N-dimethylethylenediamine (0.73 mL, 6.78 mmol) and K2CO3 (2.13 g, 15.42 mmol) in toluene (90 mL). The reaction mixture was stirred at 140° C. for 16 hours. The solvent was evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with pentane to yield 2-(benzyloxy)-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (1.8 g, 86% yield) as a white solid. C19H16FN3O2. 1H NMR (500 MHz, CDCl3) δ ppm 4.07-4.17 (m, 2H), 4.32-4.40 (m, 2H), 5.22 (s, 2H), 6.35 (s, 1H), 7.07-7.16 (m, 2H), 7.27-7.33 (m, 2H), 7.32-7.36 (m, 1H), 7.36-7.42 (m, 2H), 7.45 (d, J=7.2 Hz, 2H).

Workup

customThe solvent was evaporated in vacuo
customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70)
customThe desired fractions were collected
customthe solvents evaporated in vacuo
customthe residue triturated with pentane

Sources & evidence

ORD record: ord-9c95e9b6d9bd4732bcbe3ebcc98c7c83
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901125B2

Reaction notes

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