Triethylamine → 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-ethyl-6-nitro-4-chloro-1H-pyrazolo[3,4-b]quinoline (2.7 g, 17.8 mmol), triethylamine (3 mL, 0.02 mol), DMSO (15 mL) and 3-hydroxycyclohexylmethylamine (4.97 g, 18 mmol) was heated at 110° C. overnight. The reaction mixture was poured into ice-water (200 mL)/NH4OH (10 mL) and the solid which formed was collected by filtration. The filtrate was then extracted with CH2Cl2 (2×100 mL). The solid was stirred and sonicated with CH2Cl2 (2×200 mL) and any solids which did not go into solution were collected by filtration. All of the above CH2Cl2 filtrates and extracts were combined, washed with water and evaporated. The residue was slurried with ethyl acetate (10-15 mL)/ether (20 mL) and a red colored solid was collected by filtration and washed with ether. The solid was purified by column chromatography (2×) on silica gel (note that the solid was preloaded onto 50-100 g of silica gel) eluting with 40% THF/cyclohexane and each of the diastereomers which was isolated was dissolved in hot THF, filtered and the solvent was evaporated. Each of the residues was slurried with ethanol (5 mL), filtered and dried to afford 0.69 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1 H-pyrazolo[3,4-b]quinolin-4-amine (the RS,SR diastereomer which is labelled as Example 36(a)), m.p. 236°-238° C. and 2.23 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RR,SS diastereomer which is labelled as Example 36(b)), m.p. 247°-248° C.

Provenance & Evidence