- Environment-friendly preparation method of substituted oxazole compound
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The invention provides an environment-friendly preparation method of a substituted oxazole compound, which takes N-substituted formyl alpha-substituted glycine ester as an initial raw material; the substituted oxazole compound is obtained through a cyclization reaction under the action of a dehydrating agent such as trisubstituted phosphine dihalide, a combination of trisubstituted phosphine dihalide and an acyl halide reagent or a combination of trisubstituted phosphine oxide and an acyl halide reagent and organic amine. The obtained substituted oxazole compound can be further saponified anddecarboxylated to obtain a medical intermediate 4-substituent-5-substituent oxazole. The method can be carried out in a continuous flow manner, so that the production efficiency is improved, and the operation is reduced; a byproduct trisubstituted phosphine oxide is generated in the reaction process and can be recycled, so that the cost is reduced; phosphorus oxychloride and phosphorus pentoxide which are high in price and large in preparation process wastewater amount are not used as dehydrating agents, a high-temperature cyclization reaction is not needed, the process is simple, operation iseasy and convenient, no phosphorus-containing wastewater is discharged, and the method is environmentally friendly and low in cost. The method is high in atom economy, high in target product yield and purity and suitable for industrial application.
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Paragraph 0142-0147
(2021/01/12)
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- INTEGRASE INHIBITORS 3
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The present invention provides a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative, salt or prodrug thereof. Compounds of formula (I) are also provided.
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Page/Page column 63
(2008/06/13)
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- Synthesis of hydroxypiperidinecarboxylic acids from pyridinedicarboxylates
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(3RS,4SR,5SR)-5-Hydroxy-3-hydroxymethyl-4-piperidinecarboxylic acid 4,3′-lactone was synthesised in eight steps from ethyl glycinate via selective hydrolysis and reduction of 4,5-di-(methoxycarbonyl)-3-hydroxypyridine. The regioisomer (3RS,4RS,5SR)-5-hydr
- Damsgaard, Anders,Hazell, Rita,Bols, Mikael
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p. 521 - 527
(2007/10/03)
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- Synthesis of 4-hydroxy-6,9-difluorobenz[g]isoquinoline-5,10-diones and conversions to 4-hydroxy-6,9-bis[(aminoalkyl)amino]-benz[g]isoquinoline-5,10-diones
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Synthetic procedures have been developed which lead to 4-hydroxy-6,9-difluorobenz[g]isoquinoline-5,10-dione (4a) and its 3-methyl analogue 4b. Attempts to displace the fluorides from 4a with N,N-dimethylethylenediamine were unsuccessful. Analogue 4a on treatment with N-(t-butoxycarbonyl)ethylene diamine led to 15, formed from addition of the nucleophilic amine to C-3. On the other hand, analogue 4b, on treatment with N,N-dimethylethylenediamine led to the anticipated difluoride displacement product 3c. The protection of the hydroxy group of 4a by benzylation with phenyldiazomethane led to 4c which on treatment with N-(t-butoxycarbonyl)ethylene diamine or N,N-dimethylethylenediamine led to the corresponding 6,9-bis-substituted analogues 18a and 18b, respectively. Reductive debenzylations of 18a and 18b by hydrogenation over Pearlman's catalyst also effected partial reductions of the quinone. However, air oxidation of the over reduced products led to 3a and 3b, respectively. Treatment of 3a with hydrogen chloride gas led to the hydrochloride salt of 3d. Addition of O-p-Methoxybenzyl-N,N'-diisopropylurea to 4a led to the p-methoxybenzyl analogue 4d. Treatment of 4d with N,N-dimethylethylene diamine or N-(t-butoxycarbonyl)ethylene diamine led to displacements of the fluorides to yield 18c and 18d, respectively. Deprotection of 18c to 3b was accomplished using methanesulfonic acid. Treatment of 18d with trifluoroacetic acid followed by addition of maleic acid led to dimaleate salt of 3d.
- Krapcho,Maresch,Gallagher,Hacker,Menta,Oliva,Di Domenico,Da Re,Spinelli
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p. 1693 - 1702
(2007/10/03)
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