2- Ethoxycarbonyl-1 - tetrahydroisoquinolines

Tetrahydroisoquinolines (39) are also accessible in moderate yields using the aza-analogues 38a, b) of cyclohexenylacetonitrile 24 d). A mixture of the double-bond isomers 38 a, b) could simply be obtained in 74% yield by Knoevenagel condensation of N-methyl- or N-ethoxycarbonyl-4-piperidinone with cyanoacetic acid. 

The reaction of ethyl 2-(l,2,3,4-tetrahydroisoquinolin-l-yl)acetate hydrochloride with potassium cyanate in boiling water gave 2,3,4,6,7,116-hexahydro-1 //-pyrimido[6,1 -a]isoquinoline-2,4-dione (69IJC684). 3,4,6,7-Tetrahydro-27/-pyrimido[6,l-fl]isoquinoline-2,4-dione and its 2-thioxo derivative were prepared in the reactions of l-methyl-3,4-dihydroisoquinoline with benzoyl isocyanate and ethoxycarbonyl isothiocyanate, respectively, in the presence of NEts (75CB1541). 

The reactions of l-aminocarbonylmethylene-3,4-dihydro- and 1,2,3,4-tetrahydroisoquinolines with lV,lV-dimethylcarboxamide diethyl acetals, triethyl orthoformate, and diethyl carbonate yielded 6,7-dihydro-2//-pyrimido[6,l-a]isoquinolin-2-ones [81KFZ(5)44 82KGS1095 84JMC1470] and 9,10-dimethoxy-3,4,6,7-tetrahydro-2//-pyrimido[6,l-n]isoquinoline-2,4-dione (84JMC1470), respectively. A mixture of l-ethoxycarbonyl-9,10-dimethoxy-3,4,6,7-tetrahydro-27/-pyrimido[6,l-fl]isoquinoline-2,4-dione and l-[cyano(ethoxycarbonyl)methylene]-l,2,3,4-tetrahydroisoquinoline was obtained when 6,7-dimethoxy-l-aminocarbonylmethylene-l,2,3,4-tetrahydroisoquinoline was reacted with ethyl chloroformate in methylene chloride in the presence of pyridine (84JMC1470). 

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