4-cyano-5-carboxamide

Annulation of a cyano-carboxamide is effected in high yield by a strong base at ambient temperature. 

Chlorosulfonyl isocyanate has been used to introduce 3-carboxamide groups. The initial product, an A -chlorosulfonylcarboxamide, is treated with tri-n-butylstannanc to form the primary carboxamide[15], 3-Cyano groups can also be introduced using chlorosulfonyl isocyanate. The intermediate N-chlorosulfonylindole-3-carboxamide is converted to 3-cyanoindole on reaction with triethylamine[16] or DMF[17],... 

CONH2 amides carbamoyl cyano -amide or carboxamide ... 

Imidazole-4-catbonitrile, 5-amino-synthesis, 5, 463 Imidazolecarboxamide, cyano-reactions, 5, 436 Imidazole-4-carboxamide Hofmann reaction, 5, 435 Imidazole-4-carboxamide, 5-amino-in histidine biosynthesis, 1, 90 reactions... 

Imidazole-5-carboxamide, 4-cyano-reduction, 5, 435 synthesis, 5, 461, 472 Imidazole-5-carboxamide, 4-mercapto-oxidation, 5, 445... 

Thiophene-2-carboxamide, 3-amino-diazotization, 4, 810 Thiophene-2-carboxamide, 5-cyano-synthesis, 4, 898, 920... 

In addition to thiodiglycolic acid esters, the use of bis(cyanomethyl)sulfide in the Hinsberg reaction has facilitated the preparation of 5-cyano-thiophene-2-carboxamides. Thus, the condensation of biacetyl with bis(cyanomethyl)sulfide resulted in the efficient preparation of 10 (94% yield). 

A mixture of 14.1 parts of 1 -benzyl-4-cyano-4-piperidinopiperidine and 40 parts of 90% sulfuric acid is heated on a steam bath for 10 minutes. Without further heating, the mixture is stirred until a temperature of about 20°C is obtained. The mixture is then poured into 150 parts of ice-water and the resultant solution is alkalized with excess ammonium hydroxide solution. The aqueous solution is decanted from the precipitated oil. On treating this oil with 80 parts of acetone, crystallization sets in. After one hour the solid is filtered off and dried to yield 1 -benzyI-4-piperidinopiperidine-4-carboxamide melting at about 137.5°C to MO C. 

Other transformations of the substituents on the N-l atom were also reported <1997JOC7288> (Scheme 9) hydrolysis of the 5-cyano group of derivative 29 to a carboxamide 30 has also been reported. 

DEHYDRATION OF CARBOXAMIDE GROUPS TO CYANO GROUPS DURING ACTIVATION... 

The remaining naphthyridines, (5) and (6), have received less attention than the above many of the preparative methods for these compounds entail starting with either 4-cyanopyridines or their 3-cyano isomers, respectively, or with their carboxamide analogues. 

Synthesis By condensation of 4-piperidinopiperidine-4-carboxamide with 3,3-diphenyl-3-cyano propyl bromide (Janssen, P. (Janssen), 1961 Kleemann et al. 1999). 

Cyclization of the piperidone derivative (158) gave rise to diastereomer-ically pure perhydropyrido[2,l-h][l,3]oxazin-6-one (159) (94JA10819). Heating l-(3-methoxy-l-propyl)-2-hydroxy-3-cyano-4-methylpyridin-6(l//)-one in 25% sulfuric acid at 80°C for 2 h gave 8-methyl-6-oxo-2,3,4,6-tetrahydropyrido[2,1 -fo][ 1,3]oxazine-9-carboxamide (89EUP316779). 8-(4-Methoxyphenyl)-2,3,4,6-tetrahydropyrido[2, -b [1,3]oxazine-2,6-dione was obtained by cyclization of 3-[4-(4-methoxyphenyl)-2,6-dioxo-l,2,3,6-... 

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