CAS: 1035555-63-5; (R)-3-(2,3-Dihydroxypropyl)-6-Fluoro-5-((2-Fluoro-4-Iodophenyl)Amino)-8-Methylpyrido[2,3-D]Pyrimidine-4,7(3H,8H)-Dione

上下游产品

(R)-3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (R)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido-[2,3-d]pyrimidine-4,7(3H,8H)-dione 3-benzyl-5-(2-fluoro-4-nitrophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 3-benzyl-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione(R)-3-(2,3-dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

📜6-(甲基氨基)嘧啶-4-醇置于盐酸,Tris-(Dibenzylideneacetone)Dipalladium(0),二苯醚,水,甲酸铵,Palladium(II) Hydroxide,Potassium Carbonate,Selectfluor,4,5-双二苯基膦-9,9-二甲基氧杂蒽,Potassium Iodide,Sodium Nitrite,三氯氧磷体系中,用 四氢呋喃,乙醇,水,N,N-二甲基甲酰胺,乙腈 用作溶剂,化学反应生成Tak733抑制剂
参考文献:研究性强mek抑制剂的工艺研究和千克合成
标题:研究性强mek抑制剂的工艺研究和千克合成
摘要:Tak-733(1)是一种新型的研究性mek激酶抑制剂,带有6-氟吡啶并嘧啶酮核心.进行了1的过程研究,并开发了有效的,可扩展的路线.一个关键的中间体,即多取代的氟吡啶酮,通过三个步骤的级联反应在一个反应釜中形成:α-氟丙二酸酯和丙二腈之间的缩合,甲基酰胺的形成以及分子内环化.羟基官能团的氯化和用甲酸的环化以高收率提供了所需的吡啶并嘧啶酮核.随后的n-烷基化与(R)-甘油丙酮化物并用2-氟-4-碘代苯胺成功取代氯,收率非常好.丙酮酸官能团的最终酸催化脱保护,然后进行受控的结晶操作,得到了具有所需多晶型物的活性药物成分(api).与最初的合成方法相比,该方法更为简洁(与最初的9个步骤相比,简化了6个步骤),并且总收率得到了显着提高(从3%增至25%).这些改进使得产生的千克数为1.
Doi:10.1021/op300198A

专利信息

专利号:US-12391691-B2
优先权日:2018-11-16
标题:Synthesis of key intermediate of KRAS G12C inhibitor compound
发明人：PARSONS ANDREW THOMAS; COCHRAN BRIAN MCNEIL; POWAZINIK IV WILLIAM; CAPORINI MARC ANTHONY
权利人:AMGEN INC
摘要:The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure n nuseful for the synthesis of compounds that target KRAS G12C mutations, such as

专利号:US-2025206736-A1
优先权日:2019-11-14
标题 :Synthesis of kras g12c inhibitor compound
发明人：CORBETT MICHAEL THOMAS; CAILLE SEBASTIEN
权利人:AMGEN INC
摘要:The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

专利号:US-2025289827-A1
优先权日:2022-12-02
标 题:Morphic forms of a mutant braf degrader and methods of manufacture thereof
发明人：YU ROBERT T; HE MINSHENG; SCHNADERBECK MATTHEW J; KREGER BRIDGET; POLLOCK ROY MACFARLANE; JIANG SIYI; LI MEIQI; CHEN BOLU; LU JIANNAN
权利人:C4 THERAPEUTICS INC
摘要:Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3-[[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[1-[3-(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa-8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.

专利号:US-5411927-A
优先权日:1992-08-14
标 题 :Process of preparing composite catalysts for production of synthesis gas by oxidative conversion of methane or natural gas
发明人：CHOUDHARY VASANT R; RANE VILAS H; RAJPUT AMARJEET M R
权利人:COUNCIL SCIENT IND RES
摘要:An improved process for the production of synthesis gas (or carbon monoxide and hydrogen) by oxidative conversion of natural gas or methane, which comprises passing continuously a gaseous reactant mixture comprising methane (or natural gas) and oxygen (or air) with or without water vapors over reduced or unreduced composite catalyst, containing non-transition and/or transition metal oxides, represented by the formula Tm.Nn.R.Op, wherein T is selected from Ni, CO, Ir or the like or a mixture thereof, m is T/R mole ratio, N is a transition or non-transition element selected from Ti, Zr, Hf, Zn, Mg, Ca or the like or a mixture thereof, n represents the N/R mole ratio, R is a rare earth element selected from La, Ce, Pr, Ho, Yb or the like, or a mixture thereof, O is oxygen and p is the number of oxygen atoms required to fulfill the valence requirement of the elements in the composite catalyst. Synthesis gas can be produced in high yields and with very high production rate by oxidative conversion of methane or natural gas to CO and H2 or synthesis gas, using the composite catalyst containing non-transition and/or transition metal oxides.

专利号:US-11161823-B2
优先权日:2019-03-11
标 题 :Anticancer 1,3-dioxane-4,6-dione derivatives and method of combinatorial synthesis thereof
发明人：ISLAM IMADUL; AL-KAYSI RABIH O; BOUDJELAL MOHAMED; ALI RIZWAN; NEHDI ATEF; ALGHANEM BANDAR
权利人:NAT GUARD HEALTH AFFAIRS; KING SAUD BIN ABDULAZIZ UNIV FOR HEALTH SCIENCES; KING ABDULLAH INTERNATIONAL MEDICAL RES CENTER; KING ABDULLAH INETRNATIONAL MEDICAL RES CENTER
摘要:Compounds, methods of synthesis, and methods of cancer treatment by arylidene-1,3-dioxane-4,6-diones. A Meldrum's acid-based chemistry and hybrid solid-liquid method. The method includes protection of ketone and aldehyde components and simultaneous immobilization on the solid phase, introduction of substituents, grafts and derivatives compatible with the protection, detachment and restoration of active carbonyl reactivity, reaction of ketone library with malonate, reacting of the products with the aldehyde library in liquid phase and separation of the products by preparative HPLC.

专利号:US-2023192681-A1
优先权日:2019-11-14
标 题 :Improved synthesis of kras g12c inhibitor compound