Pyridine → N-(3-(6-bromo-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide

HRID 1799460Notes

Reaction equation

HRID 1799460 reaction equation
[Br:1][C:2]1[C:3](=[O:21])[N:4]([CH2:9][C:10]2[CH:20]=[CH:19][C:13]3[O:14][C:15]([F:18])([F:17])[O:16][C:12]=3[CH:11]=2)[C:5](=[O:8])[NH:6][N:7]=1.[C:22]([NH:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)(=[O:24])[CH3:23].N1C=CC=CC=1.C([O-])(O)=O.[Na+]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CN(C=O)C>[Br:1][C:2]1[C:3](=[O:21])[N:4]([CH2:9][C:10]2[CH:20]=[CH:19][C:13]3[O:14][C:15]([F:17])([F:18])[O:16][C:12]=3[CH:11]=2)[C:5](=[O:8])[N:6]([C:30]2[CH:31]=[C:26]([NH:25][C:22](=[O:24])[CH3:23])[CH:27]=[CH:28][CH:29]=2)[N:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 157274(3-Acetamidophenyl)boronic acidHCID 516892Sodium BicarbonateHCID 686982866-bromo-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-1,2,4-triazine-3,5(2H,4H)-dione

Product 1

HCID 68701252N-(3-(6-bromo-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamideYield 61%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

According to Scheme 2 Step 3: A mixture of 6-bromo-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-1,2,4-triazine-3,5(2H,4H)-dione (300 mg, 0.83 mmol), DMF (5 mL), 3-acetamidophenylboronic acid (222 mg, 1.24 mmol), copper acetate (150 mg, 0.83 mmol) and pyridine (135 μl, 1.66 mmol) was stirred at 65° C. for 15 hours under room atmosphere. A saturated solution of NaHCO3 (200 mL) was added and the aqueous layer was extracted thrice with 200 mL of DCM. The organic layers were combined to be dried over MgSO4, filtered and concentrated under reduced pressure to afford a brown solid. The crude solid was purified by flash chromatography with silica gel (AIT Flashmart 25 g prepacked column C18) using water/acetonitrile 6/4 as eluant to afford N-(3-(6-bromo-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide (250 mg, 61%) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted thrice with 200 mL of DCM
  2. dry with materialto be dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto afford a brown solid
  6. customThe crude solid was purified by flash chromatography with silica gel (AIT Flashmart 25 g prepacked column C18)

Sources & evidence

ORD record
ord-ca40bff29aa0435083f97ceaa7a9710c
Source dataset
uspto-grants-2013_01
Patent number
US08344138B2

Reaction notes

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