Ethyl 4-piperidinecarboxylate → Ethyl 1-(6-methylpyridazin-3-yl)piperidine-4-carboxylate

関与物質

反応手順

55 mmoles of 6-methyl-3-chloropyridazine was added to 75 mmoles of ethyl isonipecotate in 5 mL NMP and 20 mL diisopropylethylamine (DIPEA) and refluxed for 6 hours. The product was isolated as described in Example 1a above to give a 44% yield of 3-(4-carboethoxy-1-piperidinyl)-6-methylpyridazine. Reduction of 18.8 mmol of this compound using 56.6 mmol DIBAL in 100 mL THF with a Rochelle's salt quench gave 3-(4-hydroxymethyl-1-piperidinyl)-6-methylpyridazine (Formula IV: R1 =CH3 ; Y=CH2) which was used unpurified in the final step. Reaction of 5 mmol of the product described in Example 1b with 4.5 mmol of the 3-(4-hydroxymethyl-1-piperidinyl)-6-methyl pyridazine according to the procedure of Example 1c afforded after recrystallization from ethyl acetate at -70° C. the compound of formula I (R1 =R4 =CH3, Y=CH 2, R2 =R3 =hydrogen) in 12% yield, m.p. 180°-185° C.

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