Reacción #62931

Ecuación de reacción

trans octahydro-5-oxo-1(2H)-quinolinecarboxylic acid, 1,1-dimethylethyl ester

tris-(dimethylamino)methane

methanol

guanidine carbonate

→

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

Disolventes

toluene

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe solution is refluxed for 2 hours
2. 2
   ConcentraciónThe reaction mixture is concentrated
3. 3
   workup.DISSOLUTIONthe residue is dissolved in 500 ml of methanol
4. 4
   Temperaturathe reaction mixture is refluxed, under nitrogen, for 12 hours
5. 5
   ConcentraciónThe mixture is concentrated
6. 6
   Otropartitioned between brine and chloroform
7. 7
   OtroThe organic phase is separated
8. 8
   Secadodried over magnesium sulfate
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated to a yellow solid
11. 11
    OtroMedium pressure chromatography (silica gel, ethyl acetate) afforded 4.55 g (51%)
12. 12
    Otroof recovered

Procedimiento

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.).

Fuente