Potential Anticancer Agents.¹ LXIX. Tetrahydroquinazoline Analogs of Tetrahydrofolic Acid. IV. The Synthesis of 5,8-Dideaza-5,6,7,8-tetrahydroaminopterin

Abstract

The direct fusion of 4-oxocyclohexanecarboxaldehyde dimethyl acetal (III) with cyanoguanidine provided the key intermediate, 2,4-diacetamido-5,6,7,8-tetrahydro-6-quinazolinecarboxaldehyde (XV), necessary for the synthesis of 5,8-dideaza-5,6,7,8-tetrahydroaminopterin (Ila). The conversion of XV to Ila was accomplished by the reductive alkylation of p-aminobenzoyl-L-glutamic acid with XV, followed by hydrolysis of the blocked intermediate XVIII to give the crystalline and chromatographically homogeneous Ila.

The Effect of Alkyl Group Variation on the Rates of Solvolysis of Alkyl Sulphonium Halides

“…The carbon-hydrogen spin coupling constants, J C~3 -H , are considered as useful tools for the investigatio~l of s-character of the carbon atomic orbital participating in the C-H bond (1)(2)(3)(4). JIuller and Pritchard ( I ) suggested that decrease of the ring size of cycloalkanes with their C-C-C angles increased JC1sPH with the percentage of scharacter of the C-H bond, and, for example, the JC13-H of c>-clopropane exhibited the comparable value to that of the sp2 bond.…”

“…Tertiary butyl and amyl dimethylsulphonium salts have been the standard examples of the sulphonium salt series used in neutral solvolytic rate studies of this type of conlpound in the past (1). Apart from these cases the apparent hygroscopic nature of the sulphonium salts has limited the study of their solvolytic-behavior.…”

Three-Component Cycloaddition of Nitriles: Construction of Bicyclic 4-Aminopyrimidines and Their Photophysical Studies

“…Bicyclic 4-aminopyrimidines were originally obtained by introducing substituents on cyclohexanone via electrophilic substitution reactions (Scheme a) . The method was improved using dicyandiamide as the nitrogen source under a relatively high temperature (Scheme b). , The same product was obtained by reaction of 2-ethoxy-cyclohex-1-enecarbonitrile and guanidine in toluene under reflux (Scheme c). , The employment of ammonium salt, (di­chloro­meth­yl­ene)­di­meth­yl­ammonium chloride would help to increase the yield of the reaction (Scheme d) . 2,4-Dichloro-5,6,7,8-tetrahydroquinazoline can also be converted into bicyclic 4-aminopyrimidines in the presence of ammonia at 100 °C (Scheme e) .…”