- Synthesis method of 3-(2-chloroethyl)-2-methyl-4H-pyrido [1,2-a] pyrimidine-4-ketone
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The invention provides a synthesis method of 3-(2-chloroethyl)-2-methyl-4H-pyrido [1,2-a] pyrimidine-4-ketone. The method comprises the following steps: carrying out substitution reaction on ethyl acetoacetate and 1-bromo-2-chloroethane under an alkaline condition to obtain 2-acetyl-4-chlorobutyric acid ethyl ester, and reacting the 2-acetyl-4-chlorobutyric acid ethyl ester with 2-aminopyridine to obtain a risperidone intermediate 3-(2-chloroethyl)-2-methyl-4H-pyrido [1,2-a] pyrimidine-4-ketone. The method is simple to operate and suitable for industrial production. The compound 2-acetyl-4-chlorobutyric acid ethyl ester provided by the invention can be used as a raw material or an intermediate for synthesizing 3-(2-chloroethyl)-2-methyl-4H-pyrido [1,2-a] pyrimidine-4-ketone, and then risperidone is synthesized. The invention also provides an application of the compound 2-acetyl-4-chlorobutyric acid ethyl ester as an impurity reference substance of the 3-(2-chloroethyl)-2-methyl-4H-pyrido [1, 2-a] pyrimidine-4-ketone.
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Paragraph 0037-0040; 0046-0056
(2021/05/15)
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- A method for preparing risperidone chloro
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The invention discloses a method for preparing risperidone chloro, the risperidone [...] shown in structural formula II, the method comprises the following steps: a) the 2 - aminopyridine, α - acetyl - γ - butyrolactone in toluene is added, after mixing, drop added to the phosphorus oxychloride or phosphorus oxychloride in toluene solution, during the dropping control phosphorus oxychloride at a temperature between 75 - 110 °C, the completion of the dropping, thermal insulation obtained through the reaction of intermediate III 2 - methyl - 3 - (2 - chloro ethyl) - pyrido [1, 2 - a] pyrimidine - 4 - one; b) in the step a) the obtained intermediate III 2 - methyl - 3 - (2 - chloro ethyl) - pyrido [1, 2 - a] pyrimidine - 4 - one is dissolved in hydrochloric acid solution, adding palladium-carbon, the pressure of 0.20 ± 0.05 mpa the hydrogenation is carried out under the conditions of the reaction, the solution is neutralized, extraction to obtain 2 - methyl - 3 - (2 - chloroethyl) - 6, 7, 8, 9 - tetrahydro-pyrido [1, 2 - a] pyrimidine - 4 - one. The method by changing the way the reaction material, and thereby the conversion, the intermediate (III) of the yield can be up to 80 - 85%; optimize the post treatment process, and is favorable for industrial production.
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Paragraph 0031-0051
(2019/05/15)
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- Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
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Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.
- Taylor, Nicholas J.,Emer, Enrico,Preshlock, Sean,Schedler, Michael,Tredwell, Matthew,Verhoog, Stefan,Mercier, Joel,Genicot, Christophe,Gouverneur, Véronique
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supporting information
p. 8267 - 8276
(2017/06/27)
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- Synthesis of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a] pyrimidin-4-one derivatives as antibacterial agents
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A series of novel 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H- pyrido[1,2-a]pyrimidin-4-one aliphatic/ aromatic/ heterocyclic amine derivatives were synthesized in good yield. The synthesized compounds were characterized by 1H-NMR, FTIR and elemental analysis. All the synthesized compounds were screened for their in vitro antibacterial activity by agar well diffusion and micro dilution method against standard strains of Gram-Positive (Bacillus Subtilis MTCC 121 and Staphylococcus epidermidis 435), and Gram-negative (Xanthomonas Campestris 7903 and Pseudomonas aeruginosa MTCC 7908) bacteria. Compounds with substituted heterocyclic piperazine moiety showed good activity. In particular, compound 6i showed two fold better activity compared to the standard drug Strepyomycin sulphate.
- Krishnamurthy, Byregowda,Vinaya, Kambappa,Rakshith, Devraj,Prasanna, Doddakunche Shivaramu,Rangappa, Kanchugarakoppal Subbegowda
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p. 240 - 248
(2013/07/28)
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- Synthesis and in vitro antiproliferative activity of 2-methyl-3-(2- piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives against human cancer cell lines
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A series of new 2-methyl-3-(2-piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin- 4-one derivatives 6a-j were synthesized by a nucleophilic substitution reaction of 2-methyl-3-(2-piperazin-1-ylethyl)-pyrido[1,2-a]pyrimidin-4-one with various sulfonyl chlorides. The compounds were characterized by different spectral studies. All the compounds were evaluated for their antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the series, compounds 6d, 6e and 6i showed good activity on all cell lines except K562, whereas the other compounds in the series exhibited moderate activity. Compound 6d could be a potential anticancer agent and therefore deserves further research.
- Mallesha, Lingappa,Mohana, Kikkeri N.,Veeresh, Bantal,Alvala, Ravi,Mallika, Alvala
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experimental part
p. 51 - 57
(2012/07/13)
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- Synthesis of 2-methyl-3-(2-(piperazin-1-yl)ethyl)-6,7,8,9-tetrahydro- 4hpyrido[1,2-a]pyrimidin-4-one derivatives as antimicrobial agents
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A series of novel 2-methyl-3-(2-(piperazin-1-yl)ethyl)-6,7,8,9-tetrahydro- 4H-pyrido[1,2-a]pyrimidin-4-one sulfonamide and carboxamide derivatives were synthesized in good yield. The synthesized compounds were characterized by 1H-NMR, FTIR and elemental analysis. All the synthesised compounds were screened for their in vitro antimicrobial activity by agar well diffusion and micro dilution method against standard strains of Gram-positive (Bacillus subtilis MTCC 121, Staphylococcus epidermidis 435), and Gram-negative (Xanthomonas campestris 7903 and Pseudomonas aeruginosa MTCC 7908) bacteria. Compound 7a and compound 8d with dichloro substitution among sulphonamide and carboxamide series respectively showed potent inhibitory activity.
- Krishnamurthy, Byregowda,Vinaya, Kambappa,Prasanna, Doddakunche S.,Raghava, Byregowda,Rangappa, Kanchugarakoppal S.
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experimental part
p. 988 - 995
(2012/07/01)
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- An efficient route to a 5,6-dihydropyrano[3,4-b]pyridin-8-one core in two steps from enaminolactones
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A convenient two step conversion of heterocyclic enaminolactones to heterocyclic fused 2-pyran-1-ones is reported. The use of this method can be applied to a wide variety of aromatic and heteroaromatic amines to give potentially biologically active compounds in good yields.
- Sall, Cheikh,Desbois, Nicolas,Paquelet, Sandrine,Camacho, José R.,Chezal, Jean Michel,Teulade, Jean-Claude,Blache, Yves
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p. 1301 - 1304
(2008/09/18)
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- PROCESS FOR THE PREPARATION OF RISPERIDONE
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A process is provided for the preparation of risperidone of Formula (1); which process comprises reacting, in a condensation reaction, 6-fluoro-3-(4- piperidinyl)-1,2-benzisoxazole monohydrochloride of Formula (2) with 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2,a]pyrimidin-4-one monohydrochloride of Formula (3).
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Page/Page column 15
(2008/06/13)
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- METHOD FOR PREPARING RISPERIDONE
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Risperidone is prepared in a high yield by reacting 2,4-difluorophenyl(4-piperidinyl)methanone oxime hydrochloride and 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one in an aqueous alkali hydroxide solution having an alkali hydroxide concentration in the range of 20 to 40%.
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