634148-47-3

Upstream product

• 331985-92-3 N-(tert-butoxycarbonylmethyl)benzamidine hydrochloride 
• 777047-83-3 C₁₃H₁₈N₂O₂ 
• 15646-46-5 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one 

Downstream Products

• 148747-59-5 5-benzyloxycarbonylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-ylmethylcarboxylic acid 
• 873673-51-9 (5-Amino-6-oxo-2-phenyl-6H-pyrimidin-1-yl)-acetic acid methyl ester 
• 308276-59-7 [5-amino-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl]acetic acid t-butyl ester 
• 634148-49-5 2-(5-amino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)acetic acid lithium salt 
• 439910-96-0 5-amino-6-oxo-2-phenyl-1(6H)-pyrimidineacetic acid 

Relevant academic research and scientific papers

An improved synthesis of 5-acylamino-6-oxo-2-phenyl-1(6h)-pyrimidineacetic acid from glycine with readily removable protecting groups

Concise synthesis of N-acyl-5-amino-6-oxo-2-phenyl-1(6H)- yrimidineacetic acid was achieved by cyclization reaction of 2-alkyl-4- lkoxymethylene-5(4H)- oxazolone with N-(carboxymethyl)benzamidine, while a similar reaction with sodium salt of 2-alkyl-4-hydroxymethylene-5(4H)- xazolones gave a mixture of regioisomers of the pyrimidinone. N-Acyl groups (acetyl or phenylacetyl) of the pyrimidinone derivatives were readily cleaved under very mild conditions with weak base or enzyme. Thus, the process enabled us to synthesize the drug candidate without exchanging N-protecting group. Since the starting oxazolones were easily prepared from N-acylglycine, the synthetic route can be used for the large scale synthesis of the key intermediate for several enzyme inhibitors.

Syntheses of 5-amino-2-phenyl-4(3H)-pyrimidinone derivertives starting with glycine

N-Cbz derivative of 5-amino-2-phenyl-4(3H)-pyrimidinone was prepared from sodium salt of methyl hydroxymethylene glycinate and benzamidine hydrochloride in good yield. However, the reaction with N-substituted benzamidine did not proceed to give the desired pyrimidinone. In contrast, the reaction of 4-ethoxymethylene-2-phenyl-5(4H)-oxazolone readily prepared from hippuric acid and N-substituted benzamidine proceeded nicely to give 5-(benzoylamino)-6-oxo-2- phenyl-1(6H)-pyrimidineacetic acid in high yield.

PROCESS FOR PRODUCING PYRIMIDINE COMPOUND

Azlactone Compound (2) is reacted with Amidine Compound (3) to give Pyrimidine Compound (1) useful as an intermediate for enzyme inhibitors (e.g., elastase inhibitor, chymase inhibitor etc.): Pyrimidine Compound (1) Azlactone Compound (2) Amidine Compound (3) wherein each symbol is as defined in the specification.