CAS: 188416-28-6; 4-(1-Bromoethyl)-6-Chloro-5-Fluoropyrimidine

相似化合物

137234-74-3 898044-55-8 954220-98-5

上下游产品

4-chloro-6-ethyl-5-fluoropyrimidine 2,4-dichloro-6-ethyl-5-fluoropyrimidine 6-ethyl-5-fluoro-4-hydroxypyrimidine 2-fluoro-3-oxopentanoic acid ethyl ester (2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol voriconazole 3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydr°Chloride salt 2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl)pyridine-3-carboxamide

2,4-二氯-6-乙基-5-氟嘧啶置于n-溴代丁二酰亚胺(Nbs),偶氮二异丁腈,5%-Palladium/activated Carbon,氢气,三乙胺,Sodium Hydroxide,三氯氧磷体系中,用 乙醇,二氯甲烷,水 用作溶剂,40.0~90.0 °C,344.75 Kpa 条件下,反应 20.5H,反应生成4-(1-溴代乙基)-5-氟-6-氯嘧啶
参考文献:Process Development Of Voriconazole: A Novel Broad-Spectrum Triazole Antifungal Agent
标题:Process Development Of Voriconazole: A Novel Broad-Spectrum Triazole Antifungal Agent
摘要:In The Synthesis Of (2R,3S)-2-(2,4-Difluorophenyl)-3-(5-Fluoro-4-Pyrimidinyl)-1-(1H-1,2,4-Triazol-1-yl)-2-Butanol (Voriconazole),The Relative Stereochemistry Is Set In The Addition Of A 4-(1-Metalloethyl)-5-Fluoropyrimidine Derivative To 1-(2,4-Difluorophenyl)-2-(1H-1,2,4-Triazol-1-yl)-1-Ethanone,The Diastereo-Control Of This Reaction Has Been Examined By Variation Of Pyrimidine Substitution Pattern And By Changes In The Metalation And Reaction Conditions. Excellent Diastereoselection (12: Ii Is Obtained Using An Organozinc Derivative Of 6-(1-Bromoethyl)-4-Chloro-5-Fluoropyriminidine. Lifter Removal Cf The Chlorine From The Pyrimidine Ring The Absolute Stereochemistry Of Voriconazole Is Established Via A Diastereomeric Salt Resolution Process Using (1R)-10 Camphorsulfonic Acid. Synthetic Routes To The Pyrimidine Partner Have Also Been Evaluated. The Initial Six-Step Development Route From 5-Fluorouracil Has Been Superseded By A Four-Step Synthesis Involving Fluorination Of Methyl 3-Oxopentanoate And Cyclisation With Formamidine Acetate.
Doi:10.1021/op0000879

专利信息

专利号:US-10633368-B2
优先权日:2015-12-23
标 题 :Voriconazole intermediate and voriconazole synthesis method
发明人：HUANG HU; HUANG WENFENG; TU GUOLIANG; LIU JIEGEN; XU ZHONGMING; WU QIANGHUI; MENG ZHAOYANG; FANG YULING
权利人:ZHEJIANG HUAHAI PHARM CO LTD
摘要:Provided is a synthesis method for a voriconazole intermediate condensate as shown in formula II or an acid addition salt thereof. As shown in reaction formula 1, the product is prepared via compounds III and IV. The synthesis method adjusts the feeding means, and the reaction conditions are mild and controllable, thereby reducing the production of impurity A, avoiding the use of highly toxic metal lead, and eliminating the risk of highly toxic metal remaining in a drug. The product has a higher purity and significant industrial application value.

专利号:RU-2156760-C2
优先权日:1995-08-05
标 题 :Method of synthesis of triazoles, ultimate and intermediate compounds of method

专利号:CN-1076019-C
优先权日:1995-08-05
标 题:Synthesis of triazoles via addition of organometallic compounds to ketones and their intermediates