Ethyl chloroacetate → TERT-BUTYL ETHYL 2-[(TERT-BUTYL)OXYCARBONYL]BUTANE-1,4-DIOATE

Participants

Reaction Steps

As shown in Scheme I,2-alkynyl-dihydropyridazinones of the present invention can be prepared by cyclization. For example, in step A, di-t-butyl malonate and ethyl chloroacetate can be condensed in the presence of a strong base in a polar aprotic solvent to provide 1,1-di-tert-butyl 2-ethyl ethane-1,1,2-tricarboxylate. In step B, the 1,1-di-tert-butyl 2-ethyl ethane-1,1,2-tricarboxylate can be reacted the appropriate pyridine or pyrimidine acid chloride in the presence of base to provide a tricarboxylate which can be decarboxylated in step C to provide the appropriate ethyl 4-(pyridin-2-yl or pyrimidin-2-yl)-4-oxobutanoate. In step D, the appropriate ethyl 4-(pyridin-2-yl or pyrimidin-2-yl)-4-oxobutanoate can be cyclized with hydrazine to provide the appropriate 6-(pyridin-2-yl or pyrimidin-2-yl)dihydropyridazinone which can be alkylated in step E with an alkyne having an appropriate leaving group (L represents halogen or alkyl or aryl sulfonate).

Provenance & Evidence