4-Fluoroiodobenzene → HCID 86706519, compound

HRID 1396513Notes

Reaction equation

HRID 1396513 reaction equation
[CH2:1]([O:8][C:9]1[CH:19]=[C:12]2[C:13](=[O:18])[NH:14][CH2:15][CH2:16][CH2:17][N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1.CN(C)CCN>O1CCOCC1.[Cu]I>[CH2:1]([O:8][C:9]1[CH:19]=[C:12]2[C:13](=[O:18])[N:14]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:15][CH2:16][CH2:17][N:11]2[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 96054-FluoroiodobenzeneHCID 66053N,N-DimethylethylenediamineHCID 72714886HCID 72714886, compound

Product 1

HCID 86706519HCID 86706519, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Copper (I) iodide (0.02 g, 0.1 mmol) was added to a stirred suspension of 2-(benzyloxy)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one (0.5 g, 1.94 mmol), 4-iodofluorobenzene (0.63 g, 2.8 mmol) and N,N-dimethylethylenediamine (0.034 g, 0.38 mmol) in 1,4-dioxane (20 mL). The reaction mixture was stirred at 110° C. for 16 hours and then the solvent was evaporated in vacuo. The mixture was diluted with water and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by preparative-HPLC (Gemini 250 Å×20 mm, gradient ACN in water from 41% to 71% with 0.05% NH4OH in water) to yield 2-(benzyloxy)-5-(4-fluorophenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one (0.42 g, 62% yield). C20H18FN3O2. 1H NMR (400 MHz, CDCl3) δ ppm 2.35 (quin, J=6.6 Hz, 2H), 3.80 (t, J=6.3 Hz, 2H), 4.43 (t, J=6.9 Hz, 2H), 5.20 (s, 2H), 6.27 (s, 1H), 7.07-7.17 (m, 2H), 7.27-7.42 (m, 5H), 7.42-7.48 (m, 2H).

Workup

  1. customthe solvent was evaporated in vacuo
  2. additionThe mixture was diluted with water
  3. extractionextracted with AcOEt
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was purified by preparative-HPLC (Gemini 250 Å×20 mm, gradient ACN in water from 41% to 71% with 0.05% NH4OH in water)

Sources & evidence

ORD record
ord-15047058b64c4349ae7b4b15fa52dc63
Source dataset
uspto-grants-2014_12
Patent number
US08901125B2

Reaction notes

Loading…