3-Chloro-1,2-propanediol → 3-[4-[6-[[6-Methoxy-4-methyl-8-quinolinyl]amino]hexyl]-1-piperazinyl]-1,2-propanediol

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A mixture of 3 g (0.008 mole) of 6-methoxy-4-methyl-N-[6-(1-piperazinyl)hexyl]-8-quinolinamine (Example 1) and 0.72 ml (0.008 mole) of 3-chloro-1,2-propanediol was heated at 120° for 2 hours. An additional 0.2 ml of 3-chloro-1,2-propanediol and 1 ml of triethylamine were added and the mixture was heated at 130° for 3 hr and allowed to cool. The reaction mixture was diluted with ethyl acetate, washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness in vacuo. The residual oil was chromatographed over 200 g of silica gel, eluting first with one liter of a 1:15:84 mixture of triethylamine:methanol:ethyl acetate and then with a 1:20:79 mixture of the same solvents. That portion of the eluant containing fairly pure product Rf (silica--25 parts of methanol:75 parts of ethyl acetate:1 part of triethylamine)=0.26 was concentrated to dryness, taken up in 2-propanol and treated with an excess of a 17% solution of hydrogen chloride in 2-propanol to afford 0.7 g of product. That portion of the eluant containing contaminated product was concentrated and rechromatographed over 50 g of silica with a 1:15:84 mixture of triethyl amine:methanol:ethyl acetate and the product was isolated as described above. The two crops were combined and recrystallized from ethanol to afford 1.0 g (23%) of the title compound, mp. 237°-241° (dec) with prior sintering.

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