- Preparation of 2-(pyridinyl)-4-pyrimidinamines
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The process of reacting a PY-carboxamidine with α-chloroacrylonitrile in the presence of an acid-acceptor to produce 2-PY-4-pyrimidinamines where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The products produced by the process are useful as anti-allergic agents per se and, also, are useful as intermediates in the preparation of other anti-allergic agents, namely, dialkyl N-(2-PY-4-pyrimidinyl)-aminomethylenemalonates and analogs, as well as N-(2-PY-4-pyrimidinyl)ureas.
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- N-[2-(pyridinyl)-4-pyrimidinyl]ureas
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Compounds useful as anti-allergic agents are N-R3 -N-R4 -N'-R-N'-(2-Q-5-R1 -6-R2 -4-pyrimidinyl)ureas (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R1 is hydrogen, lower-alkyl or cyano, R2 is hydrogen or lower-alkyl, R3 is hydrogen, lower-alkyl or lower-hydroxyalkyl, R4 is hydrogen, lower-alkyl, lower-hydroxyalkyl, lower-alkenyl or lower-cycloalkyl. Said ureas are prepared by reacting 2-Q-4-RNH-5-R1 -6-R2 -pyrimidine (II) with a carbamylating agent selected from an R4 '-isocyanate of the formula R4 'N=C=O to produce N-R4 '-N'-R-N'-(2-Q-5-R1 -6-R2 -4-pyrimidinyl)urea (IA), an N-R3 '-N-R4 '-carbamyl halide of the formula R3 'R4 'NC(=O)-halide to produce N-R3 '-N-R4 'N'-R-N'-(2-Q-5-R1 -6-R2 -4-pyrimidinyl)urea (IB) or 1,1'-carbonyldiimidazole to produce N-(2-Q-5-R1 -6-R2 -4-pyrimidinyl)-N-R-imidazole-1-carboxamide and then reacting said 1-carboxamide with R3 R4 NH to produce I.
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- N-(2-(pyridinyl)-4-pyrimidinyl)-aminomethylenemalonates and analogs
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Compounds useful as anti-allergic agents are 2-Q-4-[XZC=C(R)NH]-5-R1 -6-R2 -pyrimidines (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R1 is hydrogen, lower-alkyl or cyano, R2 is hydrogen, lower-alkyl, hydroxy or halo, X and Z are the same or different and are each selected from lower-carbalkoxy, lower-alkanoyl, carbamyl and cyano, or STR1 where R3 and R4 are each lower-alkyl, or X is hydrogen, are prepared by reacting 4-amino-2-Q-5-R1 -6-R2 -pyrimidine (II where Q' is amino) with R'O-C-(R)=CXZ (III). Preparations of II are given. Also shown as intermediates and/or anti-allergic agents are 4-(AcNH)-2-Q-5-R1 -6-R2 -pyrimidines (IV) and 4-(R5 R6 N)-2-Q-5-R1 -6-R2 -pyrimidines (V) where Ac is lower-alkanoyl or lower-carbalkoxy, R5 is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R6 is lower-alkyl or lower-hydroxyalkyl.
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- 5,8-Dihydro-5-oxo-2-(4-or 3-pyridinyl)pyrido[2,3-d]pyrimidine-6-carboxylic acids and esters
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Antibacterial 5,8-dihydro-8-(lower-alkyl)-5-oxo-2-Q-4-R2 -6-Z-pyrido[2,3-d]pyrimidine (I) where Z is carboxy or lower-carbalkoxy, R2 is hydrogen or lower-alkyl and Q is 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents is prepared by heating di-(lower-alkyl) N-(2-Q-6-R2 -4-pyrimidinyl)aminomethylenemalonate (III) to produce 5,8-dihydro-5-oxo-2-Q-4-R2 -6-Z-pyrido[2,3-d]pyrimidine (II) which is tautomeric with 5-hydroxy-2-Q-4-R2 -6-Z-pyrido[2,3-d]pyrimidine (IIA) where Q and R2 are the same as in I above and Z is lower-carbalkoxy, reacting II(or IIA) with a lower-alkylating agent to produce I where Z is lower-carbalkoxy and hydrolyzing this ester (I) to produce I where Z is carboxy. Alternatively, the acid (II or IIA where Z is COOH) can be alkylated after first hydrolyzing the ester (II or IIA where Z is lower-carbalkoxy). The preparations of the intermediate III and intermediates used in its preparation are given.
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