Methanol → trans-2-Amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester

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Reaction Steps

To a refluxing solution, under nitrogen, of 8.89 g (35 mmol) of cis and trans octahydro-5-oxo-1(2H)-quinolinecarboxylic acid, 1,1-dimethylethyl ester, (Example 8), in 400 ml of toluene is added dropwise a solution of 6.37 g (43.8 mmol) of tris-(dimethylamino)methane in 200 ml of toluene. The solution is refluxed for 2 hours. The reaction mixture is concentrated and the residue is dissolved in 500 ml of methanol. To the methanol solution is added 12.64 g (70.1 mmol) of guanidine carbonate, and the reaction mixture is refluxed, under nitrogen, for 12 hours. The mixture is concentrated and partitioned between brine and chloroform. The organic phase is separated, dried over magnesium sulfate, filtered and concentrated to a yellow solid. Medium pressure chromatography (silica gel, ethyl acetate) afforded 4.55 g (51%) of recovered starting ketone, 0.94 g (8.8%) of (±) cis-2-amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester (Rf =0.33 (ethyl acetate)) as a foamy off-white solid, mp 178°-182° C., and 2.47 g (23%) of (±) trans-2-amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester (Rf =0.27 (ethyl acetate)) as a white solid, mp 200°-206° C. (dec.).

Provenance & Evidence