乙酰化

Methods Starting from 2-chloro-4-nitrophenol and 2- pyridine hydrochlorid, 3-chloro-4-(pyridin-2-ylmethoxy) aniline was obtained via etherization and reduction. The obtained aniline coupled with N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl) acetamide to give 4-[3-chloro-4-(2-pyridylmethoxy) phenylamino]-3-cyano-7-ethoxy-6-N-acetylaminoquinoline. And then it was deacetylated, followed by reacting with4- but-2-enoyl chloride to yield the target compound neratinib.

以2-氯－4-硝基苯酚和2-氯甲基吡啶为起始原料，经醚化、硝基还原得到3-氯－4-（吡啶－2-甲氧基）苯胺，3-氯－4-（吡啶－2-甲氧基）苯胺与3-氰基－6-乙酰氨基－7-乙氧基－4-氯喹啉反应得到3-氰基－6-乙酰氨基－4-［3-氯－4-（吡啶－2-甲氧基）苯氨基］－7-乙氧基喹啉，3-氰基－6-乙酰氨基－4-［3-氯－4-（吡啶－2-甲氧基）苯氨基］－7-乙氧基喹啉去乙酰保护基后，与-4-二甲氨基－2-丁烯酰氯经酰化反应得到ner-atinib。

Mission:"equality and mutual benefit, reputation first, unity and cooperation and friendship between the long-term" supply products: ethylenediamine; diethylamide; triethylamine; Diethylenetriamine; three ethylene diamine; three ethylene amines 40; 40 Five ethylene amines; five ethylene amines 6; caprolactam; DMF; allyl amine; N, N dimethylaniline; propylamine; are butylamine; are TOA; 3 Poly Cyanamide; 1,2 c diamine; ethanolamine; diethanolamine, triethanolamine; potassium iodide, potassium hydroxide, potassium permanganate, toluene, xylene, toluene of chlorine ; Acetone, butanone; acetylacetone; ethyl acetate, butyl acetate; Y-butyrolactone; DMC; acetyl of methyl acetate; Sanfu acetyl acid; Sanfu acetyl B Ethyl; methanol, ethanol, isopropanol; propylene glycol; glycerol; propargyl alcohol; 1.3 propylene glycol; xylitol; acetic acid; have acid; mercaptoacetic acid; vary Bitterness; adipic acid; trifluoroacetic acid; oxalic acid, the amino acid; o-amygdalin acid; DL-Acid; anhydrous piperazine; six non-piperazine, furfural, castor oil, ethylene Aldehyde; glutaraldehyde, multi-POM; isopropyl ether; anisole; tetrahydropyrrole; pure pyridine; 1.2 dichloroethane; methylene chloride, chloroform, carbon tetrachloride; hydrazine hydrate; Nonylphenol;-m-cresol; Se phenol; phenol; the tert-butyl phenol; Titanium Dioxide; iron; full Tangfen; Bisphenol A; azo two different nitrile; sodium azide; sodium carbonate ; Sodium chloride; iron oxide; cuprous chloride; thionyl chloride; D4; sodium bicarbonate; ammonia, potassium chloride; anhydrous sodium sulphite; ammonium persulfate; glycol Dingmi; B Glycol ether; calcium chloride; cyclohexanone; cyclohexane, methyl tertiary butyl ether, potassium carbonate, ferric chloride, potassium nitrate; Linsuansanna; zinc oxide; sodium nitrite; antimony oxide; Tartrate; OP-10; TX-10; tablets base; AES; sodium benzoate, sodium citrate; partial sodium silicate, sodium perborate, a sodium carbonate, sodium benzene; Asia sodium chlorate; Wuluo Care products; urea; hydrochloric acid, sulfuric acid, lactic acid; amino acid, hydrogen peroxide, ammonium bicarbonate

公司宗旨："平等互利，信誉至上，团结合作，友谊长久"乙二胺；二乙胺；三乙胺；二乙烯三胺；三乙烯二胺；三乙烯四胺；四乙烯五胺；五乙烯六胺；己内酰胺；二甲基甲酰胺；烯丙基胺；N，N二甲基苯胺；正丙胺；正丁胺；正辛胺；三聚氰胺；1，2丙二胺；一乙醇胺；二乙醇胺；三乙醇胺；碘化钾；氢氧化钾；高锰酸钾；甲苯；二甲苯；对氯甲苯；丙酮；丁酮；乙酰丙酮；醋酸乙酯；醋酸丁酯；Y-丁内酯；碳酸二甲酯；乙酰乙酸甲酯；三伏乙酰乙酸；三伏乙酰乙酸乙酯；甲醇；无水乙醇；异丙醇；丙二醇；丙三醇；丙炔醇；1.3丙二醇；木糖醇；冰醋酸；己醛酸；巯基乙酸；异辛酸；己二酸；三氟乙酸；乙二酸；对氨基苯乙酸；邻氯苦杏仁酸；DL-扁桃酸；无水哌嗪；六无哌嗪；糠醛；蓖麻油；乙二醛；戊二醛；多聚甲醛；异丙醚；苯甲醚；四氢吡咯；纯吡啶；1.2二氯乙烷；二氯甲烷；三氯甲烷；四氯化碳；水合肼；壬基酚；纯间甲酚；硒酚；苯酚；对叔丁基苯酚；钛白粉；铁粉；全糖粉；双酚A；偶氮二异丁腈；叠氮化钠；碳酸钠；氯化钠；三氧化二铁；氯化亚铜；氯化亚砜；D4；碳酸氢钠；氨水；氯化钾；无水亚硫酸钠；过硫酸铵；乙二醇丁醚；乙二醇乙醚；氯化钙；环己酮；环己烷；甲基叔丁基醚；碳酸钾；三氯化铁；硝酸钾；磷酸三钠；氧化锌；亚硝酸钠；氧化锑；酒石酸；OP-10；TX-10；粒碱；AES；苯甲酸钠；柠檬酸钠；偏硅酸钠；过硼酸钠；过碳酸钠；苯磺酸钠；亚氯酸钠；乌洛托品；尿素；盐酸；硫酸；乳酸；氨基磺酸；双氧水；碳酸氢铵

Ethoxycarbonyl-4,5-dimethyl-pyrrole (7) was prepared from ethylacetoacetate, ethyl formate and methyl ethyl ketone via oximination, Claisen condensation, and reductive condensation. The bromization of compound 7 gave 2-ethoxycarbonyl-3-bromo-4,5-dimethyl-pyrrole(8), which could be transferred to 2-ethoxy-carbonyl-3-brome-4-methyl-5-formyl-pyrrole (9) by the formolation.

由乙酰乙酸乙酯、甲酸乙酯及丁酮等原料经过肟化、Claisen缩合、还原缩合成环得到2-乙氧羰基－4，5-二甲基－吡咯(7)，溴化生成2-乙氧羰基－3-溴4，5-二甲基－吡咯(8)，最后经过甲酰化反应得到目标产物2-乙氧羰基－3-溴－4-甲基－5-甲酰基－吡咯(9)。

Mission:"equality and mutual benefit, reputation first, unity and cooperation and friendship between the long-term" supply products: ethylenediamine; diethylamide; triethylamine; Diethylenetriamine; three ethylene diamine; three ethylene amines 40; 40 Five ethylene amines; five ethylene amines 6; caprolactam; DMF; allyl amine; N, N dimethylaniline; propylamine; are butylamine; are TOA; 3 Poly Cyanamide; 1,2 c diamine; ethanolamine; diethanolamine, triethanolamine; potassium iodide, potassium hydroxide, potassium permanganate, toluene, xylene, toluene of chlorine ; Acetone, butanone; acetylacetone; ethyl acetate, butyl acetate; Y-butyrolactone; DMC; acetyl of methyl acetate; Sanfu acetyl acid; Sanfu acetyl B Ethyl; methanol, ethanol, isopropanol; propylene glycol; glycerol; propargyl alcohol; 1.3 propylene glycol; xylitol; acetic acid; have acid; mercaptoacetic acid; vary Bitterness; adipic acid; trifluoroacetic acid; oxalic acid, the amino acid; o-amygdalin acid; DL-Acid; anhydrous piperazine; six non-piperazine, furfural, castor oil, ethylene Aldehyde; glutaraldehyde, multi-POM; isopropyl ether; anisole; tetrahydropyrrole; pure pyridine; 1.2 dichloroethane; methylene chloride, chloroform, carbon tetrachloride; hydrazine hydrate; Nonylphenol;-m-cresol; Se phenol; phenol; the tert-butyl phenol; Titanium Dioxide; iron; full Tangfen; Bisphenol A; azo two different nitrile; sodium azide; sodium carbonate ; Sodium chloride; iron oxide; cuprous chloride; thionyl chloride; D4; sodium bicarbonate; ammonia, potassium chloride; anhydrous sodium sulphite; ammonium persulfate; glycol Dingmi; B Glycol ether; calcium chloride; cyclohexanone; cyclohexane, methyl tertiary butyl ether, potassium carbonate, ferric chloride, potassium nitrate; Linsuansanna; zinc oxide; sodium nitrite; antimony oxide; Tartrate; OP-10; TX-10; tablets base; AES; sodium benzoate, sodium citrate; partial sodium silicate, sodium perborate, a sodium carbonate, sodium benzene; Asia sodium chlorate; Wuluo Care products; urea; hydrochloric acid, sulfuric acid, lactic acid; amino acid, hydrogen peroxide, ammonium bicarbonate

公司宗旨：&平等互利，信誉至上，团结合作，友谊长久&乙二胺；二乙胺；三乙胺；二乙烯三胺；三乙烯二胺；三乙烯四胺；四乙烯五胺；五乙烯六胺；己内酰胺；二甲基甲酰胺；烯丙基胺；N，N二甲基苯胺；正丙胺；正丁胺；正辛胺；三聚氰胺；1，2丙二胺；一乙醇胺；二乙醇胺；三乙醇胺；碘化钾；氢氧化钾；高锰酸钾；甲苯；二甲苯；对氯甲苯；丙酮；丁酮；乙酰丙酮；醋酸乙酯；醋酸丁酯；Y-丁内酯；碳酸二甲酯；乙酰乙酸甲酯；三伏乙酰乙酸；三伏乙酰乙酸乙酯；甲醇；无水乙醇；异丙醇；丙二醇；丙三醇；丙炔醇；1.3丙二醇；木糖醇；冰醋酸；己醛酸；巯基乙酸；异辛酸；己二酸；三氟乙酸；乙二酸；对氨基苯乙酸；邻氯苦杏仁酸；DL-扁桃酸；无水哌嗪；六无哌嗪；糠醛；蓖麻油；乙二醛；戊二醛；多聚甲醛；异丙醚；苯甲醚；四氢吡咯；纯吡啶；1.2二氯乙烷；二氯甲烷；三氯甲烷；四氯化碳；水合肼；壬基酚；纯间甲酚；硒酚；苯酚；对叔丁基苯酚；钛白粉；铁粉；全糖粉；双酚A；偶氮二异丁腈；叠氮化钠；碳酸钠；氯化钠；三氧化二铁；氯化亚铜；氯化亚砜；D4；碳酸氢钠；氨水；氯化钾；无水亚硫酸钠；过硫酸铵；乙二醇丁醚；乙二醇乙醚；氯化钙；环己酮；环己烷；甲基叔丁基醚；碳酸钾；三氯化铁；硝酸钾；磷酸三钠；氧化锌；亚硝酸钠；氧化锑；酒石酸；OP-10；TX-10；粒碱；AES；苯甲酸钠；柠檬酸钠；偏硅酸钠；过硼酸钠；过碳酸钠；苯磺酸钠；亚氯酸钠；乌洛托品；尿素；盐酸；硫酸；乳酸；氨基磺酸；双氧水；碳酸氢铵

Firstly, 3-ethylthiobutanal was prepared from crotonaldehyde reacting with ethanehiol in triethylamine with high yield. Secondly, methyl acetoacetate was converted to 6-ethylthiohept-3-en-2-one by three steps via hydrolysis, condensation with 3-ethyltio-butanal and dehydration, then 6-ethylthiohept-3-en-2-one was cycloco ndensed with dimethyl malonate by Michael addition and Claisen condensation, followed by saponification and decarboxylation to give the intermediate of 5-(2-ethylthiopropyl)-cyclohexane-1,3-dione.

首先，以巴豆醛与乙硫醇为原料，在三乙胺的催化作用下高收率制得3-乙硫基丁醛；然后从乙酰乙酸甲酯出发，通过碱水解、与3-乙硫基丁醛缩合、脱水三步反应合成6-乙硫基-3-烯-2-庚酮，接着6-乙硫基-3-烯-2-庚酮与丙二酸二甲酯通过Michael加成和Claisen缩合成环，再通过皂化和脱羧反应生成中间体5-[2-丙基]-1，3-环己二酮；再与丙酸酐反应丙酰化，最后与0-3-氯-2-丙烯基羟胺肟化，得到目标化合物烯草酮。

Base played a crucial role in this reaction: in the Pd2/L1 catalyzed α-arylation of ethyl malonate, K3PO4 is the base of choice; in the α-arylation of ethyl acetoacetate, K2CO3 is the most effective base.

在这类催化反应中，碱的选择具有重要的影响：以K3PO4为碱， Pd2/L1催化体系在丙二酸二乙酯的α-芳基化中，富电子溴代芳烃显示较好的活性； Pd2/L1催化的乙酰乙酸乙酯α-芳基化时，以 K2CO3为碱，催化体系显示较好的活性，这个催化体系可控制反应得到α-芳基乙酰乙酸乙酯，而不是脱乙酰基的产物。

These data suggest that histone acetylation during nuclearremodeling (from the start of activation to the formation of pronuclei) is independent fromthe event that oocyte cytoplasm inhibits the transcription of specific genes in thedifferentiated cells, but induces reprogramming of gene expression.

这表明组蛋白的乙酰化修饰可能没有参与卵细胞质对分化细胞特有的基因转录的抑制，但引起了基因表达模式的变化。

Meanwhile,HDAC1 acetylation level is significantly increased.The overexpression of HDAC1 can promote erythroid cell proliferation and inhibits induced differentiation,the knockdown of HDAC1 or 2 inhibits erythroid cell proliferation and promotes induced differentiation.We also found that HDAC1 affects GATA1 mediated transcription activity.Thus our data revealed that HDAC1 may negatively regulate GATA1 mediated transcription and suggest that the dynamic regulation of GATA1 associated NuRD/MeCP1/HDAC1/HDAC2 complex may determine the onset of erythroid differentiation programs.Moreover,this study will eventually help to design new therapeutic approaches in treatment of leukemia.

研究发现在被诱导分化的小鼠红细胞白血病细胞中与GATA1相结合的HDAC1被乙酰化并失去活性，在血细胞中过表达HDAC1能够促进血细胞的增殖并抑制分化，反之在血细胞中敲除HDAC1或HDAC2能抑制血红细胞的增殖并促进分化，而且HDAC1能够负调控GATA1的转录活性，GATA1与NuRD/MeCP1复合体之间的动态调控，决定血红细胞分化的发生和发展，并为探索白血病的致病机理奠定了理论基础。

The invention is characterized in that the carrier is produced through the reaction between halogen acetylized crosslinked polystyrene resin and hydroxybenzyl alcohol.

本发明的特征是：该载体由卤乙酰化聚苯乙烯树脂与对羟基苯甲醇反应制得。

This hyperacetylation causes cell cycle arrest and cell death in cancer cells but not in normal cells.

这种高度乙酰化造成癌症细胞的细胞周期阻断和细胞死亡，而不造成正常细胞的细胞周期阻断和细胞死亡。

According to the clear water experiment, aeration performance of the new equipment is good with high total oxygen transfer coefficient and oxygen utilization ratio.

曝气设备的动力效率在叶轮转速为120rpm～150rpm时取得最大值，此时氧利用率和充氧能力也具有较高值。

The environmental stability of that world - including its crushing pressures and icy darkness - means that some of its most famous inhabitants have survived for eons as evolutionary throwbacks, their bodies undergoing little change.

稳定的海底环境─包括能把人压扁的压力和冰冷的黑暗─意谓海底某些最知名的栖居生物已以演化返祖的样态活了万世，形体几无变化。