1,4-Dioxane → HCID 72714885, compound

HRID 1396514Notes

Reaction equation

HRID 1396514 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.BrC1C=CC=C([F:27])N=1.C[N:29]([CH3:33])[CH2:30][CH2:31]N.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1[CH2:47][CH2:46]OCC1>[Cu]I>[CH2:1]([O:8][C:9]1[CH:19]=[C:12]2[C:13](=[O:18])[N:14]([C:33]3[CH:47]=[CH:46][C:31]([F:27])=[CH:30][N:29]=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

7

Reactant 5

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 66053N,N-DimethylethylenediamineHCID 6394382-Bromo-6-fluoropyridineHCID 72714886HCID 72714886, compound

Product 1

HCID 72714885HCID 72714885, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
80 °C

Procedure

Copper (I) iodide (0.011 g, 0.057 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 (0.3 g, 1.16 mmol), 2-bromo-6-fluoropyridine (0.25 g, 1.42 mmol), N,N-dimethylethylenediamine (0.02 g, 0.23 mmol) and K3PO4 (0.5 g, 2.36 mmol) in 1,4-dioxane (15 mL). The reaction mixture was stirred at 80° C. for 16 hours and then the solvent was evaporated in vacuo. The mixture was diluted with water and extracted with DCM. 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 40% to 70% with 0.05% NH4OH in water) to yield 2-(benzyloxy)-5-(5-fluoropyridin-2-yl)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one (0.151 g, 37% yield). C19H12FN4O2. 1H NMR (400 MHz, CDCl3) δ ppm 2.40 (quin, J=6.7 Hz, 2H), 4.18 (t, J=6.3 Hz, 2H), 4.35 (t, J=6.9 Hz, 2H), 5.21 (s, 2H), 6.28 (s, 1H), 7.30-7.42 (m, 3H), 7.43-7.50 (m, 3H), 8.12 (dd, J=9.3, 4.0 Hz, 1H), 8.26 (d, J=3.0 Hz, 1H).

Workup

  1. customthe solvent was evaporated in vacuo
  2. additionThe mixture was diluted with water
  3. extractionextracted with DCM
  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 40% to 70% with 0.05% NH4OH in water)

Sources & evidence

ORD record
ord-40f865fb0b8f4d62912f409e9c347041
Source dataset
uspto-grants-2014_12
Patent number
US08901125B2

Reaction notes

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