反应详情

A mixture of 4-hydroxycyclohexylmethylamine (2.2 g, 17.05 mmol), 1-ethyl-4-chloro-6-methoxy-1H-pyrazolo[3,4-b]quinoline (2.0 g, 7.66 mmol) and DMSO was heated at 110°-120° C. under a nitrogen atmosphere for 16 hours. The reaction mixture was poured into ice-water and the mixture was extracted with CH2Cl2 (4×50 ml). The organic layers were combined, dried over MgSO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with CH2Cl2 /methanol (9/1), followed by a second silica gel column eluting with ethyl acetate to afford 1.3 g of crude product. The crude product was dissolved in warm methanol, cooled to room temperature and treated with an equivalent amount of methanesuflonic acid. Ether was added to the mixture and the solid which formed was collected by filtration, washed with ether and recrystallized from isopropanol to afford 0.85 g of 1-ethyl-6-methoxy-N-(4-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine.CH3SO3H, as yellow crystals, m.p. 256°-258° C. (dec.).

1. temperaturewas heated at 110°-120° C. under a nitrogen atmosphere for 16 hours
2. extractionthe mixture was extracted with CH2Cl2 (4×50 ml)
3. dry with materialdried over MgSO4
4. customevaporated to dryness
5. customThe residue was purified by column chromatography on silica gel eluting with CH2Cl2 /methanol (9/1)
6. washeluting with ethyl acetate
7. customto afford 1.3 g of crude product
8. additiontreated with an equivalent amount of methanesuflonic acid
9. customthe solid which formed
10. filtrationwas collected by filtration
11. washwashed with ether
12. customrecrystallized from isopropanol