Pyridine → N-(3-(4-(4-chlorobenzyl)-6-bromo-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide

HRID 1624877Notes

Reaction equation

HRID 1624877 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[C:12](=[O:13])[C:11]([Br:14])=[N:10][NH:9][C:8]2=[O:15])=[CH:4][CH:3]=1.[C:18]([NH:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)(=[O:20])[CH3:19].N1C=CC=CC=1.CC#N>CN(C=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[C:12](=[O:13])[C:11]([Br:14])=[N:10][N:9]([C:26]3[CH:27]=[C:22]([NH:21][C:18](=[O:20])[CH3:19])[CH:23]=[CH:24][CH:25]=3)[C:8]2=[O:15])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6342AcetonitrileHCID 157274(3-Acetamidophenyl)boronic acidHCID 687033544-(4-chlorobenzyl)-6-bromo-1,2,4-triazine-3,5(2H,4H)-dione2×

Product 1

HCID 68702221N-(3-(4-(4-chlorobenzyl)-6-bromo-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamideYield 62%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

According to Scheme 2 Step 3: To a stirred solution of 4-(4-chlorobenzyl)-6-bromo-1,2,4-triazine-3,5(2H,4H)-dione (0.400 g) and 2(B) (411 mg, 1.3 mmol) in DMF (5 mL) were successively added of the 3-acetamidophenylboronic acid (0.34 g, 1.9 mmol), copper(II) acetate (0.23 g, 1.3 mmol) and 0.20 g of pyridine (2.5 mmol). The mixture was stirred overnight at 60° C. The reaction mixture was quenched with a saturated sodium bicarbonate solution and extracted with ethyl acetate (×3). The combined organic layers were washed successively with water, brine, dried over MgSO4, filtered and concentrated. The crude product was purified by C18 reverse phase column, 65 g column: 20% CH3CN gradient 20 to 60% to afford 0.350 g (yield=62%) of N-(3-(4-(4-chlorobenzyl)-6-bromo-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide 2(C).

Workup

  1. customThe reaction mixture was quenched with a saturated sodium bicarbonate solution
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined organic layers were washed successively with water, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by C18 reverse phase column, 65 g column

Sources & evidence

ORD record
ord-fc3a9adadaf94c9699e708bdde99a8f3
Source dataset
uspto-grants-2014_07
Patent number
US08779129B2

Reaction notes

Loading…