A Convenient Synthesis of 3-(1-Aminoalkyl)quinolin-2(1
 H
 )-one Derivatives

Kobayashi, Kazuhiro; Fuchimoto, Yuhei; Hayashi, Kazutaka; Mano, Masaaki; Tanmatsu, Miyuki; Morikawa, Osamu; Konishi, Hisatoshi

doi:10.1055/s-2005-872086

Cited by 6 publications

(2 citation statements)

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“…The solvent was evaporated and the residual solid was purified by recrystallization (Et 2 O-THF) to give 3a as a white solid; yield: 0.18 g (67%); mp 229-230 °C (dec). C,67.84;H,5.99;N,16.66. Found: C,67.82;H,5.98;N,16.58.…”

Section: (Z)-nn-dimethyl-2-[7-methyl-2-oxo-1-phenyl-23-dihydropyridmentioning

confidence: 99%

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Two-Step Synthesis of (Z)-2-[2-Oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetamide Derivatives from 2-Chloro-6-methylpyridine-3-carbonitrile

Kobayashi¹,

Iitsuka²,

Morikawa³

et al. 2007

Synthesis

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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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Section: (Z)-nn-dimethyl-2-[7-methyl-2-oxo-1-phenyl-23-dihydropyridmentioning

confidence: 99%

“…Calcd for C 22 H 25 N 5 O 2 : C,67.50;H,6.44;N,17.89. Found: C,67.49;H,6.69;N,17.80 C,61.24;H,5.38;N,17.00. Found: C,61.10;H,5.58;N,16.97.…”

Section: (Z)-nn-dimethyl-2-[7-methyl-2-oxo-1-phenyl-23-dihydropyridmentioning

confidence: 99%

Two-Step Synthesis of (Z)-2-[2-Oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetamide Derivatives from 2-Chloro-6-methylpyridine-3-carbonitrile

Kobayashi¹,

Iitsuka²,

Morikawa³

et al. 2007

Synthesis

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Preparation and Reactivity of Magnesium Enolates

Grison

2009

Patai's Chemistry of Functional Groups

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Acid–Base and Solvation properties of Metal Enolates. Part 1: The Enolate Ion and Main‐Group Metal Enolates

Bastos

2017

Patai's Chemistry of Functional Groups

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A Convenient Synthesis of 3-(1-Aminoalkyl)quinolin-2(1 H )-one Derivatives

Cited by 6 publications

References 1 publication

Two-Step Synthesis of (Z)-2-[2-Oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetamide Derivatives from 2-Chloro-6-methylpyridine-3-carbonitrile

Two-Step Synthesis of (Z)-2-[2-Oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetamide Derivatives from 2-Chloro-6-methylpyridine-3-carbonitrile

Preparation and Reactivity of Magnesium Enolates

Acid–Base and Solvation properties of Metal Enolates. Part 1: The Enolate Ion and Main‐Group Metal Enolates

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