Pyrido[1,2‐<i>a</i>]pyrimidines; New chemical entities in medicinal chemistry

Hermecz, István

doi:10.1002/med.2610080204

Cited by 43 publications

(17 citation statements)

References 75 publications

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“…A number of tetrahydropyrido[1,2-a]pyrimidones with pharmacological activity 1 have been synthesized and some of them are already available as commercial products. Mass spectral data concerning various substituted pyrido [1,2-a]pyrimidines have already been published.…”

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confidence: 99%

Electron-impact Induced Fragmentation of the Isomeric 2- and 4-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidines

Takácsy¹,

Tamás²,

Hermecz³

et al. 1997

Rapid Commun. Mass Spectrom.

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The mass spectrometric behaviour of the isomeric 2-and 4-oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidines have been studied in detail under electron-impact induced ionization. Differences in the main fragmentation routes of the two isomeric compounds have been established by high resolution mass measurements and linked scan spectra (constant B/E) of the deuterium-labelled analogue. Correlation between the different dominating tautomeric forms and the characteristic fragmentation pattern of the isomers is discussed. © 1997 by John Wiley & Sons, Ltd. Received 12 December 1996; Revised 10 February 1997; Accepted 13 February 1997 Rapid. Commun. Mass Spectrom. 11, 664-666 (1997 2-8 The fragmentation routes of the substituted compounds mainly involve scissions of the substituents while the ring system mostly remains intact. These facts prompted us to study in detail the mass spectrometric behaviour of the two unsubstituted isomers, compounds 1 and 2, as isomeric skeletons for this group of heterocycles. EXPERIMENTALCompounds 1 and 2 were synthesised from the corresponding 3-ethoxycarbonyl derivatives 9 by hydrolysis and decarboxylation.10 To obtain the labelled analogue, compound 2 was treated with D 2 O and the efficiency of the labelling was checked using the 12 eV electron impact (EI) mass spectrum to avoid the formation of [M -1] + ions. The EI mass spectra were recorded and exact mass measurements (resolution (R) = 7000) were carried out using a VG (Fisons, Manchester, UK) TS-250 type mass spectrometer with a direct inlet system. Linked scan spectra at constant B/E were obtained using an MS-902 mass spectrometer (Kratos, Manchester, UK).The structures of the synthesized compounds were confirmed by infrared and nuclear magnetic resonance and mass spectrometric data. RESULTS AND DISCUSSIONThe mass spectra of the two isomers recorded at various ionizing energies (Table 1) exhibited molecular ions as the base peak in every spectrum, but the molecular ion of isomer 1 appeared to be much more stable than that of isomer 2. The lower the ionizing energy was, the greater the difference became. When the main fragmentation routes are compared the difference between the two compounds becomes even more striking. As the high resolution data and the metastable daughter ion spectra of the molecular ions (Tables 1 and 2, respectively) show, the fragmentation of the M + . ion of 2 is related mostly to the saturated pyridine ring (losses of neutrals such as hydrogen, alkyl or alkenyl radicals or olefin molecules) i.e. having a high similarity to that of piperidine.11,12 The decomposition of the M + . ion of 1 is much more selective: the only significant process is the primary loss of a CO molecule from ring B via contraction of the ring. Similar behaviour was also found to exist for 2-pyridone 9,12 and pyrido[2,3-d]pyrimidine-4(3H)-one. 13The observed differences in the EI fragmentation of isomers 1 and 2 are in accordance with their very different physico-chemical properties. For instance the melting point of 1 and that of many ...

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confidence: 99%

Electron-impact Induced Fragmentation of the Isomeric 2- and 4-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidines

Takácsy¹,

Tamás²,

Hermecz³

et al. 1997

Rapid Commun. Mass Spectrom.

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“…calcd for C 24 H 14 FN 5 OS: C 65.59,H 3.21,N 15.94;found C 65.64,H 3.27,N 15.97. 6-(4-Fluorophenyl)-9-phenylamino-5H-thiazolo [3',2':2, 3]pyrido [4,5-d] 4,158.9,152.5,151.1,149.8,149.4,146.5,144.9,133.1,131.1,130.5,129.4,127.7,124.4,122.7,121.3,120.5,117.6,115.98,102.5;IR (KBr) ν max : 3346 (N-H), 1682 (C＝O) cm -1 . Anal.…”

Section: Synthesis Of 2-mentioning

confidence: 99%

“…Polyheterocycles are vital structural motifs with numerous applications in pharmaceutical and material science. [1] Among them, pyrido[1,2-a]pyrimidines were classified as natural and non-natural products, which exhibited potential biological properties, [2] such as tranquilizer, [3] analgesics, [4] antipsychotics, [5] and anti-HIV agents. [6] In particular, the 4H-pyrido[1,2-a]pyrimidin-4one skeleton is a privileged scaffold in medicinal chemistry, which has shown broad biological activities.…”

Section: Introductionmentioning

confidence: 99%

Iodine-Dimethyl sulfoxide Promoted Synthesis of Novel TetracyclicThiazolo[3',2':2,3]pyrido[4,5-d]pyrido[1,2-a]pyrimidinones

Xu¹,

Zhang²,

Zhang³

et al. 2019

Chinese Journal of Organic Chemistry

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An iodine-dimethyl sulfoxide (I 2-DMSO) promoted efficient method is described for the synthesis of thiazolo-[3',2':2,3]pyrido[4,5-d]pyrido[1,2-a]pyrimidin-5-ones (5) via Pictet-Spengler cyclization. The key intermediate, 2-(3-amino-5-phenylaminothiazolo-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3), was readily prepared from 2-chloromethyl-4H-pyrido-[1,2-a]pyrimidin-4-one (1) and potassium N-phenyl-N'-cyano-imido-thiocarbonate (2) by Thorpe-Ziegler isomerization. The novel synthetic method offers the advantage of mild reaction conditions, operational simplicity and higher yields.

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“…For related literature, see: Hermecz & Meszaros (1988); Doria et al (1983); Colpaert (2003); Knoll et al (1987); Kozlovskaya et al (1995); Hermecz et al (1996, and references therein). For ring conformation puckering parameters, see: Cremer & Pople (1975).…”

Section: Related Literaturementioning

confidence: 99%

8-(4-Fluorophenyl)-11,11-dimethyl-5,9-dioxo-6,8,9,10,11,12-hexahydro-5H-quinolino[1,2-a]quinazoline-7-carbonitrile dimethylformamide solvate

Jiang

Cao

et al. 2007

Acta Cryst E

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Pyrido[1,2‐a]pyrimidines; New chemical entities in medicinal chemistry

Cited by 43 publications

References 75 publications

Electron-impact Induced Fragmentation of the Isomeric 2- and 4-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidines

Electron-impact Induced Fragmentation of the Isomeric 2- and 4-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidines

Iodine-Dimethyl sulfoxide Promoted Synthesis of Novel TetracyclicThiazolo[3',2':2,3]pyrido[4,5-d]pyrido[1,2-a]pyrimidinones

8-(4-Fluorophenyl)-11,11-dimethyl-5,9-dioxo-6,8,9,10,11,12-hexahydro-5H-quinolino[1,2-a]quinazoline-7-carbonitrile dimethylformamide solvate

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