Synthesis of N-[4-[2-(2,4-Diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)-ethylamino]benzoyl]-L-glutamic acid. An acyclic analogue of 5,6,7,8-tetrahydrofolic acid

The synthesis of N-4-2-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)ethylamino]benzoyl]-L-glutamic acid ( 2 ), a two carbon analogue of 5-DACTHF ( 1 ) and an acyclic analogue of 5,6,7,8-tetrahydrofolic acid, is reported. The pyrimidinylacetaldehyde diethyl acetal 3 , which was prepared in 2-steps from 2-chloro acetaldehyde diethyl acetal, was converted to 2 in four steps. Compound 2 was less cytotoxic toward Detroit 98 or L cells than 5-DACTHF ( 1 ).