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).