反应详情

To a solution of 1-methyl-1H-pyrazole-5-carboxylic acid (5.28 g, 41.9 mmol) in dichloromethane (55 ml) was added oxalyl chloride (9.14 ml, 104.8 mmol) followed by 3 drops of dimethylformamide. The reaction was stirred at room temperature for 18 hours before concentration in vacuo. The residue was dissolved in acetonitrile (42 ml) and added dropwise to a cooled solution of 3-(2-chloro-5-methoxyphenyl)pyridine-2,6-diamine (preparation 1, 9.5 g, 38 mmol) and lutidine (6.6 ml, 57.1 mmol) in acetonitrile (650 ml). The reaction was allowed to warm to room temperature and stirred under nitrogen for 2 hours. The reaction was quenched by the addition of water (300 ml) and concentrated to low volume in vacuo. The aqueous residue was washed with dichloromethane (2×300 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with ethylacetate:heptane 1:4 to furnish a solid. This was recrystallised from toluene (100 ml) to afford 6.7 g of the title product.

1. temperatureto warm to room temperature
2. stirringstirred under nitrogen for 2 hours
3. customThe reaction was quenched by the addition of water (300 ml)
4. concentrationconcentrated to low volume in vacuo
5. washThe aqueous residue was washed with dichloromethane (2×300 ml)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel column chromatography
9. washeluting with ethylacetate:heptane 1:4
10. customto furnish a solid
11. customThis was recrystallised from toluene (100 ml)