New Synthesis of Pyrido[2,3-d]pyrimidines. I. Reaction of 6-Alkoxy-5-cyano-3,4-dihydro-2-pyridones with Guanidine and Cyanamide

Abstract

The first step of a new synthesis of pyrido[2,3-d]pyrimidines.

4-Amino-2-arylamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7-(8H)-ones as BCR kinase inhibitors for B lymphoid malignancies

“…Thus, 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridin-3-carbonitriles (10) are obtained by reaction of an a,b-unsaturated ester (8) and malonitrile (9) in NaOMe/MeOH [15]. Treatment of pyridones 10 with guanidine systems (11, R 4 ¼ H, alkyl, aryl) affords 4-amino-pyrido[2,3-d]pyrimidines (12, R 4 ¼ H, alkyl, aryl) [16].…”

Crystal structure analysis of 5‐amino‐7‐(pyrrolidin‐1‐yl)‐2,4,4‐trimethyl‐1,4‐dihydro‐1,6‐naphthyridine‐8‐carbonitrile

“…The synthetic approach of some pyridine derivatives from tetracyanopropenes are important part of cyanocarbon chemistry and the synthesis of 1, 6-napthyridine derivatives have been widely dealt in the literature [9,10] as part of a general study on cyclization of dinitriles. The applications of malanonitrile in organic chemistry for the synthesis of unique heterocyclic systems which have pharmaceutical applications such as pesticides, fungicides are well known [11].…”

N-Cyanoimines in the Synthesis of Heterocyclic Compounds. (Review)

“…The aroylketene dimers were isolated from the reaction mixture in addition to the oxazinones 35, indicating that the C≡N bond in cyanoimines has lower reactivity than in cyanamides [32]. When heated with hydrobromic acid, the N-cyanoimine 25 undergoes cyclization to 5-amino-7-bromo-4-methyl-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one 38 [21]. Compounds 18 and 19 are hydrolyzed similarly [18].…”

“…When 5-cyano-6-methoxy-4-methyl-3,4-dihydro-2-pyridone is boiled with cyanamide in dioxane in the presence of sodium and the product is treated with the stoichiometric amount of hydrochloric acid in absolute ethanol or methanol, 5-cyano-6-cyanoimino-4-methyl-3,4-dihydro-2-pyridone (25) is obtained. According to the PMR spectra, it exists in equilibrium with the 6-cyanoimino form [21]. The reaction of the N-oxides of substituted 1,2,4-triazines with cyanamide in the presence of bases gives the corresponding triazinylcyanamide, which exists predominantly in the cyanoimino form 27 [23].…”