Synthesis of Substituted 2-AminonicotinonitrilesMono-, di-, and trisubstituted 2-aminonicotinonitriles 8, 13, 14, and 19 are prepared from ketonic Munnich-bases hydrochlorides 4 . HCI, enones 12, P-aminovinylketones 17, 3-aminoacroleines 18, vinamidinium perchlorates 21, and 3,3-diaminoacrylonitrile (3). generated in situ.

Die Aminolyse des Cyanketen-0,N-Aceta-Gemisches 1 Z/E mit den Aminen 2a,b fiihrt zu den E-konfigurierten primar/sekundiiren Cyanketenaminalen 3a,b. Durch Reaktion von 3a,b mit den 1.3-Biselektrophilen 4, 6a,b, 9 HCI, 12, 13,15a,b, 17 und 19 lassen sich die N2-substituierten 2-Aminonicotinonitrile 5, 7, 8, 10, 11, 14, 16 und 20 herstellen. Umsetzung der 2-Aminonicotinonitrile mit a-Phenylethylrest in Position 2 (14b, 16a, 8a, 20b, 5 und 8b) mit Polyphosphorsaure fuhrt zu den primiiren 2-Aminonicotinonitrile Zla-f.

Two strategies towards the synthesis of Iso-Piritrexim (12) are described. A) The Mannich-reaction of ketone 2 yields the bases 4-HCl and 5-HCl. By means of LC base 4 is separated and treated with in situ generated 3,3-diaminoacrylonitrile (9) to yield the 2-aminonicotinonitrile 11. The cyclocondensation of 11 with guanidine provides Iso-PTX (12). B) Reduction and oxidation of the beta-ketoester 15 leads to the beta-ketoaldehyde 17, which is cyclocondensed with 2,4,6-triaminopyrimidine (18) to yield Iso-PTX (12). In the NCl-tumor-test Iso-PTX (12) shows a moderate activity against some leukemia and lung cancer cell lines.

Synthesis of Substituted 2-Aminonicotinonitriles.-In order to create new substitution patterns in the 2-aminonicotinonitrile series compounds of type (III), (VI), and (IX) are synthesized which are potential precursors for the preparation of medicinically interesting heterocycles. -(TROSCHUETZ, R.; DENNSTEDT, T.; Arch. Pharm. (Weinheim, Ger.) 327 (1994) 1, 33-40; Inst. Pharm. Lebensmittelchem., Univ.

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