Dimethylformamide → N-(3-(4-(4-chlorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)-2-methoxyacetamide

HRID 1624908Notes

Reaction equation

HRID 1624908 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:13](=[O:14])[N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[C:11](=[O:23])[C:10]([O:24][CH3:25])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.C(N(C(C)C)CC)(C)C.[CH3:40][O:41][CH2:42][C:43](Cl)=[O:44]>C(=O)([O-])[O-].[Na+].[Na+]>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][N:12]2[C:11](=[O:23])[C:10]([O:24][CH3:25])=[N:9][N:8]([C:4]3[CH:3]=[C:2]([NH:1][C:43](=[O:44])[CH2:42][O:41][CH3:40])[CH:7]=[CH:6][CH:5]=3)[C:13]2=[O:14])=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 687024682-(3-aminophenyl)-4-(4-chlorobenzyl)-6-methoxy-1,2,4-triazine-3,5(2H,4H)-dione

Product 1

HCID 59139888N-(3-(4-(4-chlorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)-2-methoxyacetamideYield 70%

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Procedure

According to Scheme 9 Step 2: A mixture of 2-(3-aminophenyl)-4-(4-chlorobenzyl)-6-methoxy-1,2,4-triazine-3,5(2H,4H)-dione (100 mg, 0.28 mmol), DMF (4 mL), diisopropylethylamine (95 μl, 0.56 mmol) and methoxyacetyl chloride (30 μl, 0.33 mmol) was stirred under nitrogen at room temperature during 1 hour. The mixture was diluted with 50 mL of a saturated solution of sodium carbonate and the aqueous layer was extracted twice with 50 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 (Merck Flashmart prepacked column 15 g SiO2) using AcOEt/cyclohexane 4/6 as eluant to afford a beige solid. The solid was washed with diethylether to afford N-(3-(4-(4-chlorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)-2-methoxyacetamide 4.141 (84 mg, 70%) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted twice with 50 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 (Merck Flashmart prepacked column 15 g SiO2)
  7. customto afford a beige solid
  8. washThe solid was washed with diethylether

Sources & evidence

ORD record
ord-b664b83c8577486cb1fb9906d9d1f44b
Source dataset
uspto-grants-2014_07
Patent number
US08779129B2

Reaction notes

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