Z)-2- pyrimidin-4(1H)-ylidene]acetamides were prepared using a twostep sequence. The first step was the addition of magnesium enolates of tertiary acetamides to 2-chloro-6-methylpyridine-3-carbonitrile to give vinylogous urea derivatives, (Z)-3-amino-3-(2-chloro-6-methylpyridin-3-yl)propenamides. In the second step, these were reacted with aryl isocyanates in the presence of sodium hydride to give the corresponding pyrido[2,3-d]pyrimidin-2(1H)-one derivatives.Pyrido[2,3-d]pyrimidin-2(1H)-one derivatives have attracted medical interest due to their biological activities. 1a,b,d,e However, very little work has been reported on the general synthesis of these derivatives. 1 Therefore, the development of new methods for the synthesis of these derivatives is meaningful. We now report a two-step route to a new pyrido[2,3-d]pyrimidin-2(1H)-one system 3. The first step of the sequence involves the addition of magnesium enolates of tertiary acetamides to 2-chloro-6-methylpyridine-3-carbonitrile (1), leading to the formation of (Z)-3-amino-3-(2-chloro-6-methylpyridin-3-yl)propenamides 2. The second step creates the pyrimidinone ring system by sodium hydride mediated reaction with aryl isocyanates, in which the chloro function acts as a leaving group. To the best of our knowledge, this 2-[2-oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetic acid system is unknown in the literature.The addition of magnesium amide enolates to the cyano carbon of 1 was readily achieved and afforded good yields of the corresponding (Z)-3-amino-3-(2-chloro-6-methylpyridin-3-yl)propenamide derivatives 2, as shown in Scheme 1. The Z-configuration of the adducts was assigned by analogy with earlier results; 2a,b the hydrogenbonding interactions between the C=O group of the amide and 3-amino groups (see spectral data below) makes the Z-isomers thermodynamically more stable.The subsequent tandem addition-cyclization sequence between 2 and isocyanates was expected to afford the desired (Z)-2-[2-oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetamide derivatives 3. As shown in Scheme 1, the reactions were carried out by successive treatment of 2 with two equivalents of sodium hydride and one equivalent of aryl isocyanates in N,N-dimethylformamide at room temperature. Following workup and recrystallization, the desired products were isolated. The results for the ring-closure step are summarized in Table 1, which indicates that generally fair-to-good yields were obtained. The Z-configuration of the products 3 was deduced from their 1 H NMR and infrared spectra. The 1 H NMR spectra showed signals assigned to N-H at much lower magnetic field (d = 12.47-12.61), which is attributed to the hydrogen bonding interactions between the C=O of the amide and the amino group. The infrared spectra of 3 showed absorption bands that are assigned to the C=O of the amide at much lower wavenumber values (1626-1636 cm -1 ). This assignment was strongly supported by NOE experiments of product 3g. Thus, irradiation of the signal at d = 5.68, which was assigned to...

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methylthiophenyl isocyanides were synthesized from 2-aminobenzenethiols and were shown to undergo ring closure to 2,4-disubstituted 4H-1,4-benzothiazine derivatives by deprotonation of the hydrogen adjacent to the sulfur atom with sodium hydride or potassium tert-butoxide, followed by trapping with various electrophiles.

A simple method for synthesizing 1-aryl-4-hydroxy-N,N-dimethyl-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxam-ides has been developed. Thus, 3-(2-chloropyridin-3-yl)-N,N-dimethyl-3-oxopropanamide, easily prepared by treating ethyl 2-chloropyridine-3-carboxylate with lithium enolate of N,N-dimethylacetamide, smoothly reacts with a range of aryl isocyanates in the presence of two molar amounts of sodium hydride to provide the desired products in moderate yields.