根据句意及所给首字母提示，写出正确单词。
1. It’s dangerous for animals to drink if the water_百度知道
根据句意及所给首字母提示，写出正确单词。
1. It’s dangerous for animals to drink if the water
&&&2;&&nbsp. The nose of the elephant is about two meters l &&&&&&&&nbsp. Some animals are g &&&3;&&&&&&&nbsp.&&1;&&&& ．&&&&&nbsp. It’s dangerous for animals to drink if the water become p &&
and friendly to people．&&
;&nbsp，写出正确单词;&nbsp. This is a babital that has never been d
根据句意及所给首字母提示
提问者采纳
&nbsp.gentle&nbsp. polluled& 3;&nbsp
1.discovered&& 4; 2
其他类似问题
为您推荐：
等待您来回答
下载知道APP
随时随地咨询
出门在外也不愁RESEARCH CATEGORIES
FREE REFERENCE ENTRIES
Worldmark Encyclopedia of the States
Dictionary of American HistoryThe Columbia Encyclopedia, 6th ed.Cities of the United States
Further reading
Facts and information from other sites
Related topics
For students and teachers
< provides students and teachers facts, information, and biographies from verified, citable sources, including:
Trending topics
For students and teachers
< provides students and teachers facts, information, and biographies from verified, citable sources, including:
For students and teachers
< provides students and teachers facts, information, and biographies from verified, citable sources, including:& Tesaglitazar, AZ-242, AR-H039242XX, Galida,-2, 2515
Tesaglitazar, AZ-242, AR-H039242XX, Galida,-2, 2515
摘 要：Tesaglitazar, AZ-242, AR-H039242XX, Galida,-2, -5 (undefined isomer),C20-H24-O7-S,2(S)-Ethoxy-3-[4-[2-[4-(methylsulfonyloxy)phenyl]ethoxy]phenyl]propionic acid
【药物名称】Tesaglitazar, AZ-242, AR-H039242XX, Galida
【化学名】2(S)-Ethoxy-3-[4-[2-[4-(methylsulfonyloxy)phenyl]ethoxy]phenyl]propionic acid
【CAS登记号】-2, -5 (undefined isomer)
【结构式】
【分子式】C20-H24-O7-S
【分子量】408.4686
【原研厂家】AstraZeneca (Originator)
【作用类别】Antidiabetic Drugs, ENDOCRINE DRUGS, Treatment of Diabetic Complications, Type 2 Diabetes Mellitus, Agents for, PPARalpha Agonists, PPARgamma Agonists
【研发状态】Phase III
【合成情况】　
〖来源〗Drugs Fut
〖合成路线〗
〖标题〗Tesaglitazar
〖合成方法〗The reaction of 2-(4-hydroxyphenyl)ethyl alcohol (I) with Ms-Cl and TEA in dichloromethane gives the bis-methanesulfonate (II), which is condensed with 4-hydroxybenzaldehyde (III) by means of K2CO3 in acetonitrile to yield the substituted benzaldehyde (IV). The condensation of (IV) with phosphonium salt (V) by means of tetramethylguanidine (TMG) in chloroform affords the acrylic ester (VI), which is reduced with H2 over Pd/C in ethyl acetate to provide the propionic ester (VII). The hydrolysis of (VII) with LiOH in THF/water gives the propionic acid (VIII) as a racemic mixture, which is condensed with (R)-phenylglycinol (IX) by means of EDC, HOBt and DIEA in dichloromethane to yield the amide (X) as a diastereomeric mixture that is separated by crystallization and chromatography. The desired (S)-isomer (XI) is treated with H2SO4 in hot dioxane/water to furnish the target propionic acid.
〖作者〗McIntyre, J.A.; Castaer, J.; Bays, M.
〖参考〗McIntyre, J.A.; Castaer, J.; Bays, M.; Tesaglitazar. Drugs Fut , 959
〖出处〗Drugs Fut):959
〖来源〗Drugs Fut
〖合成路线〗
〖标题〗Tesaglitazar
〖合成方法〗The condensation of 4-(benzyloxy)benzaldehyde (XII) with phosphonium salt (V) by means of TMG as before gives the acrylic ester (XIII), which is hydrogenated with H2 over Rh/C in methanol to yield the propionic ester (XIV). The hydrolysis of (XIV) with LiOH in dioxane/water affords the corresponding acid (XV) as a racemic mixture, which is condensed with (R)-phenylglycinol (IX) by means of EDC, HOBt and DIEA in dichloromethane to provide the amide (XVI) as a diastereomeric mixture that is separated by crystallization and chromatography. The desired (S)-isomer (XVII) is treated with H2SO4 in hot dioxane/water to furnish the chiral propionic acid (XVIII), which is esterified with EtOH and HCl to give the ethyl propionate (XIX). The hydrogenolysis of the benzyl ether group of (XIX) with H2 over Pd/C in ethyl acetate yields the phenolic derivative (XX), which is condensed with the bis-methanesulfonate by means of K2CO3 in acetonitrile to afford the adduct (XXI). Finally, the ester group of (XXI) is hydrolyzed with LiOH in THF/water to provide the target propionic acid.
〖作者〗McIntyre, J.A.; Castaer, J.; Bays, M.
〖参考〗McIntyre, J.A.; Castaer, J.; Bays, M.; Tesaglitazar. Drugs Fut , 959
〖出处〗Drugs Fut):959
〖来源〗Drugs Fut
〖合成路线〗
〖标题〗Tesaglitazar
〖合成方法〗Reaction of chloroacetic acid (XXII) with sodium ethoxide (XXIII) in ethanol gives 2-ethoxyacetic acid ethyl ester (XXIV), which is condensed with 4-methoxybenz-aldehyde (XXV) by means of t-BuOK in THF to yield 2-ethoxy-3-(4-methoxyphenyl)-2-propenoic acid ethyl ester (XXVI). Hydrolysis of ester (XXVI) with NaOH in hot ethanol/water affords the propenoic acid derivative (XXVII), which is reduced with H2 over Pd/C in ethanol to provide racemic 2-ethoxy-3-(4-methoxyphenyl)propionic acid (XXVIII). Optical resolution of mixture (XXVIII) is performed by salt formation with 1(S)-(1-naphthyl)ethylamine (XXIX) followed by crystallization to give the diastereomeric salt (XXX), which is treated with NaOH, followed by acidification with HCl to yield 2(S)-ethoxy-3-(4-methoxyphenyl)propionic acid (XXXI). Demethylation of compound (XXXI) by reaction with NaOH and octanethiol in NMP affords 2(S)-ethoxy-3-(4-hydroxyphenyl)propionic acid (XXXII), which is esterified with ethanol/HCl to provide the corresponding ethyl ester (XXXIII). Condensation of ester (XXXIII) with the bismesylate (II) by means of either K2CO3 in 2-butanone or Na2CO3 in acetone provides 2(S)-ethoxy-3-[4-[2-[4-(methanesulfonyloxy)-phenyl]ethoxy]phenyl]propionic acid ethyl ester (XXI), which is finally hydrolyzed with NaOH or LiOH in acetone/water.
〖作者〗McIntyre, J.A.; Castaer, J.; Bays, M.
〖参考〗McIntyre, J.A.; Castaer, J.; Bays, M.; Tesaglitazar. Drugs Fut , 959
〖出处〗Drugs Fut):959
〖来源〗EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872
〖合成路线〗
〖标题〗New 3-aryl-2-aryl propionic acid derivs. and analogs
〖合成方法〗The reaction of 2-(4-hydroxyphenyl)ethyl alcohol (I) with Ms-Cl and TEA in dichloromethane gives the bis-methanesulfonate (II), which is condensed with 4-hydroxybenzaldehyde (III) by means of K2CO3 in acetonitrile to yield the substituted benzaldehyde (IV). The condensation of (IV) with phosphonium salt (V) by means of tetramethylguanidine (TMG) in chloroform affords the acrylic ester (VI), which is reduced with H2 over Pd/C in ethyl acetate to provide the propionic ester (VII). The hydrolysis of (VII) with LiOH in THF/water gives the propionic acid (VIII) as a racemic mixture, which is condensed with (R)-phenylglycinol (IX) by means of EDC, HOBt and DIEA in dichloromethane to yield the amide (X) as a diastereomeric mixture that is separated by crystallization and chromatography. The desired (S)-isomer (XI) is treated with H2SO4 in hot dioxane/water to furnish the target propionic acid.
〖作者〗Andersson, K.; Boije, M.; Inghardt, T.; Lindstedt Alstermark, E.-L.; Gottfries, J.; Li, L. (AstraZeneca plc)
〖参考〗Andersson, K.; Boije, M.; Inghardt, T.; Lindstedt Alstermark, E.-L.; Gottfries, J.; Li, L. (AstraZeneca plc); New 3-aryl-2-aryl propionic acid derivs. and analogs. EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872
〖出处〗EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872,,():
〖来源〗EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872
〖合成路线〗
〖标题〗New 3-aryl-2-aryl propionic acid derivs. and analogs
〖合成方法〗The condensation of 4-(benzyloxy)benzaldehyde (XII) with phosphonium salt (V) by means of TMG as before gives the acrylic ester (XIII), which is hydrogenated with H2 over Rh/C in methanol to yield the propionic ester (XIV). The hydrolysis of (XIV) with LiOH in dioxane/water affords the corresponding acid (XV) as a racemic mixture, which is condensed with (R)-phenylglycinol (IX) by means of EDC, HOBt and DIEA in dichloromethane to provide the amide (XVI) as a diastereomeric mixture that is separated by crystallization and chromatography. The desired (S)-isomer (XVII) is treated with H2SO4 in hot dioxane/water to furnish the chiral propionic acid (XVIII), which is esterified with EtOH and HCl to give the ethyl propionate (XIX). The hydrogenolysis of the benzyl ether group of (XIX) with H2 over Pd/C in ethyl acetate yields the phenolic derivative (XX), which is condensed with the bis-methanesulfonate by means of K2CO3 in acetonitrile to afford the adduct (XXI). Finally, the ester group of (XXI) is hydrolyzed with LiOH in THF/water to provide the target propionic acid.
〖作者〗Andersson, K.; Boije, M.; Inghardt, T.; Lindstedt Alstermark, E.-L.; Gottfries, J.; Li, L. (AstraZeneca plc)
〖参考〗Andersson, K.; Boije, M.; Inghardt, T.; Lindstedt Alstermark, E.-L.; Gottfries, J.; Li, L. (AstraZeneca plc); New 3-aryl-2-aryl propionic acid derivs. and analogs. EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872
〖出处〗EP 1084101; EP 1084102; EP 1084103; WO 9962870; WO 9962871; WO 9962872,,():
〖来源〗WO 0296865
〖合成路线〗
〖标题〗Process for the preparation 3-aryl-2-hydroxypropionic acid deriv.
〖合成方法〗Reaction of chloroacetic acid (XXII) with sodium ethoxide (XXIII) in ethanol gives 2-ethoxyacetic acid ethyl ester (XXIV), which is condensed with 4-methoxybenz-aldehyde (XXV) by means of t-BuOK in THF to yield 2-ethoxy-3-(4-methoxyphenyl)-2-propenoic acid ethyl ester (XXVI). Hydrolysis of ester (XXVI) with NaOH in hot ethanol/water affords the propenoic acid derivative (XXVII), which is reduced with H2 over Pd/C in ethanol to provide racemic 2-ethoxy-3-(4-methoxyphenyl)propionic acid (XXVIII). Optical resolution of mixture (XXVIII) is performed by salt formation with 1(S)-(1-naphthyl)ethylamine (XXIX) followed by crystallization to give the diastereomeric salt (XXX), which is treated with NaOH, followed by acidification with HCl to yield 2(S)-ethoxy-3-(4-methoxyphenyl)propionic acid (XXXI). Demethylation of compound (XXXI) by reaction with NaOH and octanethiol in NMP affords 2(S)-ethoxy-3-(4-hydroxyphenyl)propionic acid (XXXII), which is esterified with ethanol/HCl to provide the corresponding ethyl ester (XXXIII). Condensation of ester (XXXIII) with the bismesylate (II) by means of either K2CO3 in 2-butanone or Na2CO3 in acetone provides 2(S)-ethoxy-3-[4-[2-[4-(methanesulfonyloxy)-phenyl]ethoxy]phenyl]propionic acid ethyl ester (XXI), which is finally hydrolyzed with NaOH or LiOH in acetone/water.
〖作者〗Ioannidis, P.; Ehrl, R.; MacKintosh, W. (AstraZeneca AB)
〖参考〗Ioannidis, P.; Ehrl, R.; MacKintosh, W. (AstraZeneca AB); Process for the preparation 3-aryl-2-hydroxypropionic acid deriv.. WO 0296865
〖出处〗WO 0296865,,():
本文导航：
Tesaglitazar, AZ-242, AR-H039242XX, Galida,-2, 2515
上一篇：暂无}