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

Temperature

50 °C

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.

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

ORD record

ord-cc3a76a9f2354e539d293d64c1930add

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08779129B2