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

HRID 1799458Notes

Reaction equation

HRID 1799458 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:12](=[O:13])[C:11](Br)=[N:10][N:9]([C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:24])[CH3:23])[CH:18]=[CH:19][CH:20]=3)[C:8]2=[O:25])=[CH:4][CH:3]=1.[CH2:28]1[CH2:32]OC[CH2:29]1.C(COC)OC.[Cl-].C([Zn+])(C)C>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:12](=[O:13])[C:11]([CH:28]([CH3:32])[CH3:29])=[N:10][N:9]([C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:24])[CH3:23])[CH:18]=[CH:19][CH:20]=3)[C:8]2=[O:25])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 80711,2-DimethoxyethaneHCID 68702221N-(3-(4-(4-chlorobenzyl)-6-bromo-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamideHCID 178461829HCID 178461829, compound

Product 1

HCID 59139834N-(3-(4-(4-chlorobenzyl)-6-isopropyl-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamideYield 58%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

According to Scheme 2 Step 4: A mixture 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) (100 mg, 0.22 mmol), THF (2 mL), dimethoxyethane (69 μl, 0.67 mmol) and PdCl2(dppf) (8 mg, 0.011 mmol). was stirred under nitrogen atmosphere at 50° C. Isopropylzinc(II) chloride solution 0.58M (1.15 mL, 0.67 mmol) was added dropwise and the mixture was stirred at 50° C. during 1 hour. The reaction mixture was diluted with 100 mL of water and extracted twice with 100 mL of CH2Cl2. The combined organic layers were 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 brown solid. The solid was washed with diisopropylether and was filtered to afford N-(3-(4-(4-chlorobenzyl)-6-isopropyl-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide (53 mg, 58%) as a white solid.

Workup

  1. stirringthe mixture was stirred at 50° C. during 1 hour
  2. extractionextracted twice with 100 mL of CH2Cl2
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a brown solid
  7. customThe crude solid was purified by flash chromatography with silica gel (Merck Flashmart prepacked column 15 g SiO2)
  8. customto afford a brown solid
  9. washThe solid was washed with diisopropylether
  10. filtrationwas filtered

Sources & evidence

ORD record
ord-56cf2b5cf63b44c084d6b4c537e1ffba
Source dataset
uspto-grants-2013_01
Patent number
US08344138B2

Reaction notes

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