Cesium carbonate → 3-[({5-[(4-Fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile

HRID 571732

Reaction equation

HRID 571732 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([OH:29])[CH:28]=[C:22]3[CH2:21]2)=[O:19])=[CH:14][CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.O>[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([N:20]2[CH2:25][CH2:24][N:23]3[N:26]=[C:27]([O:29][CH2:2][C:3]4[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=4)[C:6]#[N:7])[CH:28]=[C:22]3[CH2:21]2)=[O:19])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 178519627HCID 178519627, compound

Product 1

HCID 727032163-[({5-[(4-Fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrileYield 59.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

3-(bromomethyl)benzonitrile (0.086 g, 0.44 mmol) was added to a stirred suspension of 5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ol (0.105 g, 0.4 mmol) and Cs2CO3 (0.261 g, 0.8 mmol) in ACN (2 mL). The mixture was stirred at room temperature for 16 hours, then diluted with water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with DIPE to yield 3-[({5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl}oxy)methyl]benzonitrile (0.089 g, 59% yield) as a white solid. C21H17FN4O2. 1H NMR (500 MHz, CDCl3) δ ppm 4.08 (br. s., 4 H), 4.74 (br. s., 2 H), 5.22 (s, 2 H), 5.51 (br. s., 1 H), 7.15 (t, J=8.5 Hz, 2 H), 7.44-7.51 (m, 3 H), 7.60 (d, J=7.8 Hz, 1 H), 7.65 (d, J=7.8 Hz, 1 H), 7.74 (s, 1 H).

Workup

  1. extractionextracted with DCM
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo
  9. customthe residue triturated with DIPE

Sources & evidence

ORD record
ord-01c8c94e1b9646b7944fc260fa3cbca8
Source dataset
uspto-grants-2015_05
Patent number
US09029366B2

Linked notes

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