219908-84-6

Upstream product

• 872-85-5 pyridine-4-carbaldehyde 
• 219908-82-4 3-carbomethoxy-2-chloro-4-diethoxymethylpyridine 
• 27443-46-5 4-diethoxymethylpyridine N-oxide 
• 27443-40-9 4-(diethoxymethyl)pyridine 
• 58481-11-1 methyl 2-chloroisonicotinate 
• 13726-52-8 diethyl N-(p-aminobenzoyl)-L-glutamate 
• 219908-83-5 5-diethoxymethyl-5-deazapterin 
• 118287-89-1 2-chloro-4-diethoxymethylpyridine 

Relevant academic research and scientific papers

Synthesis of protected 5-formylpyrido[2,3-d] pyrimidine via a 2,3,4-trisubstituted pyridine using an ortho-litmation strategy; applicationtothe synthesis of a folate derivative

A convenient route for the preparation of a protected 5-formylpyrido[2,3-d]pyrimidine from 2,3,4-trisubstituted pyridines has been developed. The readily available diethylacetal of pyridinc 4-carboxaldehyde is chlorinated at the 2-position and then treated with LDA and methyl chloroformate to give a 2,3,4-trisubstituted pyridine (12). Treatment of 12 with guanidine hydrochloride gives the pyrido[23-rf]pyrimidine in good yield. A 4-aminobenzoylglutamic acid side chain is installed by means of a reductive amination step to provide a 5-substituted derivative that is, after deprotection, a confonnationally unrestricted analog of 5,10-methylenetetrahydrofolate(1), the natural co-factor for thymidylate synthase, an important chemotherapeutic target in the treatment of cancer.