反应详情

Potassium tert-butoxide (2.6 ml, 1.0 M in THF) is added to a mixture of cis-3,5-dimethylpiperazino 2-chloroquinoline-4-carboxamide (X, 704 mg), tert-butyl isocyanoacetate (IX, 390 mg) and DMF (10 ml) at -78°. The mixture is stirred for 1 hr at -78° and is allowed to warm to 20-25° over several hours. After stirring at 20-25° for 16 hrs, water is added and the mixture extracted several times with ethyl acetate, the combined organic phases are dried over magnesium sulfate, filtered, and concentrated to provide a mixture of product and starting material, which is resubmitted to the above conditions (THF used instead of DMF). Purification of the resultant crude material by flash chromatography (silica gel; ethyl acetate/methanol (4/1)) provides the product. Recrystallization from hot ethyl acetate/hexane gives the desired title compound, mp 233-234°; IR (mineral oil) 1719, 1615, 1607, 1388, 1270, 1128 cm-1 ; NMR (CDCl3) 8.67, 7.95-8.15, 7.65-7.9, 7.54, 4.7-4.85, 3.35-3.55, 2.4-3.1, 1.68, 1.22 and 0.85-1.05 δ; MS (EI, m/e) 408, 351, 335, 307, 239, 195 and 113.

1. temperatureto warm to 20-25° over several hours
2. stirringAfter stirring at 20-25° for 16 hrs
3. extractionthe mixture extracted several times with ethyl acetate
4. dry with materialthe combined organic phases are dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto provide
8. additiona mixture of product
9. customPurification of the resultant crude material by flash chromatography (silica gel; ethyl acetate/methanol (4/1))
10. customprovides the product
11. customRecrystallization from hot ethyl acetate/hexane