Ethyl nicotinate amide from

A second route to ricinine was suggested by the observation that ethyl 2 4-dihydroxy-6-methyl-nicotinate is obtained from the condensation of ethyl malonate and ethyl /3-aminocrotonate in the presence of sodium ethylate (59). This substituted ethyl nicotinate when converted to the amide by means of alcoholic ammonia and dehydrated with phosphorus oxychloride gives rise to 2 4-dichloro-3-cyano-6-methylpyridine (LXXXYIII). Condensation of LXXXVIII with benzaldehyde followed by oxidation yields the acid (LXXXIX) and this on treatment with sodium methylate... 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Nicotinic acid (pyridine-3-carboxylic acid), mp 236°C, was first obtained by oxidation of the alkaloid nicotine by KMn04. It is produced commercially from 5-ethyl-2-methylpyridine (see p 291). Nicotinic acid and its amide belong to the B group of vitamins (vitamin B5). The daily requirement of an adult is ca. 20 mg. Deficiency of nicotinic acid causes pellagra, a skin disease. 

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