CAS: 877399-51-4; (R)-Tert-Butyl 4-(4-(6-Amino-5-(1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy)Pyridin-3-yl)-1H-Pyrazol-1-yl)Piperidine-1-Carboxylate

该化合物是一个复杂的有机化合物,其特点是多功能结构,具有管状环,有助于其基本性和形成氢结带的潜力.一个箱状酸碱酸碱的存在意味着酸性,而酯性功能表明它可以进行水解.该化合物还含有一个丙烯和丙烯环,可能具有芳香特性并影响其反应性和溶解性.苯基组的二氯和氟基子替代成分会加强其亲和性,并可能影响其生物活动.总体而言,该化合物可能具有重大的药理特性,使其对药用化学,特别是治疗剂的开发具有兴趣.其复杂的结构表明它可能与生物目标发生相互作用,因此有必要对其有效性和安全性进行进一步调查.

英文名称(R)-Tert-Butyl 4-(4-(6-Amino-5-(1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy)Pyridin-3-yl)-1H-Pyrazol-1-yl)Piperidine-1-Carboxylate
中文名称克里唑替尼中间体
IUPAC名称tert-butyl (R)-4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate
其它别名Tert-Butyl 4-[4-(6-Amino-5-{[(1R)-1-(2,6-Dichloro-3-Fluorophenyl)Ethyl]Oxy}-3-Pyridinyl)-1H-Pyrazol-1-Yl]-1-Piperidinecarboxylate; Crizotinib Impurity 23; Tert-Butyl 4-[4-[6-Amino-5-[(1R)-1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy]Pyridin-3-Yl]Pyrazol-1-Yl]Piperidine-1-Carboxylate; 1-Piperidinecarboxylic Acid,4-[4-[6-Amino-5-[(1R)-1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy]-3-Pyridinyl]-1H-Pyrazol-1-Yl]-, 1,1-Dimethylethyl Ester; 4-[4-[6-Amino-5-[[(R)-1-(2,6-Dichloro-3-Fluorophenyl)Ethyl]Oxy]Pyridin-3-Yl]Pyrazol-1-Yl]Piperidine-1-Carboxylic Acid Tert-Butyl Ester; (R)-Tert-Butyl 4-(4-(6-Amino-5-(1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy)Pyridin-3-yl)-1H-Pyrazol-1-yl); Tert-Butyl 4-(4-(6-Amino-5-((R)-1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy)Pyridin-3-yl)-1H-Pyrazol-1-yl)Piperidine-1-Carboxylate; (R)-Tert-Butyl 4-(4-(6-Amino-5-(1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy)Pyridine -3-yl)-1H-Pyrazol-1-yl)Piperidine-1-Carboxylate (R)-Tert-Butyl 4-(4-(6-Amino-5-(1-(2,6-Dichloro-3-Fluorophenyl)Ethoxy)Pyridine -3-yl)-1H-Pyrazol-1-yl)Piperidine-1-Carboxylate
CAS编号877399-51-4
MFCD编号:MFCD18207062
FDA UNII编号:5R7WMG535E
分子式:C26H30Cl2FN5O3
分子量:550.45
产品CID: 1885994
产品分类医药中间体 → 原料药中间体

相似结构搜索
InChIKey: QDGJKKNXEBCNJI-OAHLLOKOSA-N
QDGJKKNXEBCNJI-OAHLLOKOSA-N…
计算化学: 氢键受体数7.0氢键供体数1.0可旋转键数7.0

MSDS等安全信息

GHS符号GHS07
警示词Warning
危险描述H302-H315-H319-H335
防范说明P261-P305+P351+P338

上下游产品

4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (S)‐1‐(2,6-dichloro-3-fluorophenyl)ethanol 5-bromo-3-[1 (R)-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine crizotinib

合成工艺路线路线简述

24424-99-5 + 877399-52-5 = 877399-51-4
反应条件:1.1 Solvents: Tetrahydrofuran; 2 H,Rt
标题:Development And Biological Investigations Of Hypoxia-Sensitive Prodrugs Of The Tyrosine Kinase Inhibitor Crizotinib
作者:Bielec,Bjoern; Et Al
参考文献:Bioorganic Chemistry 日期:2020 卷标:99]

877399-00-3 + 877399-74-1 = 877399-51-4
反应条件:1.1 Reagents: Cesium Carbonate Catalysts: [1,1′-Bis(Diphenylphosphino)Ferrocene]Dichloropalladium Solvents: 1,2-Dimethoxyethane,Water; 3 H,90 °C
标题:Structure Based Drug Design Of Crizotinib (Pf-02341066),A Potent And Selective Dual Inhibitor Of Mesenchymal-Epithelial Transition Factor (C-Met) Kinase And Anaplastic Lymphoma Kinase (Alk)
作者:Cui,J. Jean; Et Al
参考文献:Journal Of Medicinal Chemistry 日期:2011 卷标:54(18) 页码:6342-6363]

877399-00-3 + 1472039-37-4 = 877399-51-4
反应条件:1.1 Reagents: Potassium Fluoride,Polyethylene Glycol Lauryl Ether Catalysts: Triphenylphosphine,Tetrabutylammonium Chloride,Cuprous Iodide,2604409-93-8 Solvents: Water; 24 H,55 - 60 °C
标题:Mild And Robust Stille Reactions In Water Using Parts Per Million Levels Of A Triphenylphosphine-Based Palladacycle
作者:Takale,Balaram S.; Et Al
参考文献:Angewandte Chemie 日期:2021 卷标:60(8) 页码:4158-4163]

1195-66-0 + 877399-73-0 = 877399-51-4
反应条件:1.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; -10 °C; 2 H,Rt1.2 -2.1 Reagents: Cesium Carbonate Catalysts: Tetrabutylammonium Bromide,Dichloro[1,1′-Bis(Diphenylphosphino)Ferrocene]Palladium(Ii) Dichloromethane Addu... Solvents: Toluene,Water; 6 H,80 °C
标题:Improved Synthesis Of Crizotinib
作者:Zhang,Guang-Yan; Et Al
参考文献:Zhongguo Yaowu Huaxue Zazhi 日期:2014 卷标:24(6) 页码:445-449]

1195-66-0 + 877399-73-0 = 877399-51-4
反应条件:1.1 Reagents: Chloro(1-Methylethyl)Magnesium Solvents: Tetrahydrofuran; 255 Min,-10 °C; -10 °C -> 20 °C; 1 H,20 °C1.2 Solvents: Tetrahydrofuran; 105 Min,20 - 30 °C; 9 H,25 °C2.1 Reagents: Cesium Carbonate Catalysts: Tetrabutylammonium Bromide,[1,1′-Bis(Diphenylphosphino)Ferrocene]Dichloropalladium Solvents: Toluene,Water; 22 °C; 22 °C -> 70 °C; 4.5 H,70 °C
标题:Fit-For-Purpose Development Of The Enabling Route To Crizotinib (Pf-02341066)
作者:De Koning,Pieter D.; Et Al
参考文献:Organic Process Research & Development 日期:2011 卷标:15(5) 页码:1018-1026]

24424-99-5 + 877399-52-5 = 877399-51-4
反应条件:1.1 Solvents: Tetrahydrofuran; 12 H,Rt
标题:Reactive Oxygen Species (Ros)-Sensitive Prodrugs Of The Tyrosine Kinase Inhibitor Crizotinib
作者:Bielec,Bjoern; Et Al
参考文献:Molecules 日期:2020 卷标:25(5)]

1428264-35-0 = 877399-51-4
反应条件:1.1 Reagents: Methylamine Solvents: Ethanol; 20 Min,Rt
标题:Ortho-Substituent Effect Promoted Rapid Cleavage Of Amide C-N Bond Under Mild Conditions
作者:Wang,Peng; Et Al
参考文献:Research On Chemical Intermediates 日期:2014 卷标:40(8) 页码:2935-2943]

1448326-33-7 + 2249892-26-8 = 877399-51-4
反应条件:1.1 Reagents: Cesium Carbonate Catalysts: Palladium Diacetate,Phosphine,Bis(1,1-Dimethylethyl)Methyl-,Tetrafluoroborate(1-) (1:1) Solvents: 1,4-Dioxane; 18 H,120 °C
标题:Heterocyclic Allylsulfones As Latent Heteroaryl Nucleophiles In Palladium-Catalyzed Cross-Coupling Reactions
作者:Markovic,Tim; Et Al
参考文献:Journal Of The American Chemical Society 日期:2018 卷标:140(46) 页码:15916-15923]

877399-00-3 + 3144-16-9 = 877399-51-4
反应条件:1.1 Reagents: Potassium Hydroxide Solvents: Heptane,Tert-Butyl Methyl Ether,Water2.1 Reagents: Cesium Carbonate Catalysts: Tetrabutylammonium Bromide,[1,1′-Bis(Diphenylphosphino)Ferrocene]Dichloropalladium Solvents: Toluene,Water; 22 °C; 22 °C -> 70 °C; 4.5 H,70 °C
标题:Fit-For-Purpose Development Of The Enabling Route To Crizotinib (Pf-02341066)
作者:De Koning,Pieter D.; Et Al
参考文献:Organic Process Research & Development 日期:2011 卷标:15(5) 页码:1018-1026]

15128-82-2 + 330156-50-8 = 877399-51-4
反应条件:1.1 Reagents: Triphenylphosphine Solvents: Tetrahydrofuran; Rt -> 0 °C1.2 Reagents: Diethyl Azodicarboxylate; 0 °C; 3 H,Rt2.1 Reagents: Iron,Hydrochloric Acid Solvents: Ethanol; Rt -> Reflux; 1 H,Reflux3.1 Reagents: N-Bromosuccinimide Solvents: Acetonitrile; Rt -> 0 °C; 15 Min,0 °C4.1 Reagents: Sodium Carbonate Catalysts: Dichlorobis(Triphenylphosphine)Palladium Solvents: Dimethylformamide,Water; Rt -> 87 °C; 16 H,87 °C; 87 °C -> Rt
标题:Method For Preparing C-Met Inhibiter Pf22341066
参考文献:China]

2179-57-9 + 877399-50-3 = 877399-51-4
反应条件:1.1 Reagents: Butyllithium Solvents: Tetrahydrofuran,Hexane; -78 °C; 15 Min,-78 °C1.2 10 Min,-78 °C; 10 Min,-78 °C; -78 °C -> Rt; 1 H,Rt1.3 Reagents: M-Chloroperbenzoic Acid Solvents: Dichloromethane; 15 Min,0 °C; 16 H,0 °C1.4 Reagents: Sodium Bicarbonate Solvents: Dichloromethane,Water; 1 H,Rt2.1 Reagents: Cesium Carbonate Catalysts: Palladium Diacetate,Phosphine,Bis(1,1-Dimethylethyl)Methyl-,Tetrafluoroborate(1-) (1:1) Solvents: 1,4-Dioxane; 18 H,120 °C
标题:Heterocyclic Allylsulfones As Latent Heteroaryl Nucleophiles In Palladium-Catalyzed Cross-Coupling Reactions
作者:Markovic,Tim; Et Al
参考文献:Journal Of The American Chemical Society 日期:2018 卷标:140(46) 页码:15916-15923

1-(2,6-二氯-3-氟苯基)乙醇置于bis-Triphenylphosphine-Palladium(II) Chloride,N-溴代丁二酰亚胺(Nbs),Boc-L-脯氨酸,铁粉,Sodium Carbonate,对甲苯磺酸,溶剂黄146,盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺,三苯基膦,偶氮二甲酸二乙酯体系中,用四氢呋喃,四氯化碳,乙醇,二氯甲烷,水,N,N-二甲基甲酰胺作为反应溶剂,化学反应 22.0H,反应生成克里唑替尼中间体
参考文献:一种抗肿瘤分子靶向药物克里唑替尼的合成工艺方法
标题:一种抗肿瘤分子靶向药物克里唑替尼的合成工艺方法
摘要:本发明为一种新的抗肿瘤分子靶向药物克里唑替尼的合成工艺方法,涉及克里唑替尼前体的手性异构体的拆分工艺优化和副产物回收利用.本发明采用boc-L-脯氨酸(n-叔丁氧基羰基-L-脯氨酸)与催化剂对甲苯磺酸和缩合剂1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐相组合的催化拆分方法,将1-(2,6-二氯-3-氟代苯基)乙醇消旋体拆分为s-型醇和r-型醇,将拆分副产物混合物水解,并进行构型转换,制得s型醇1-(2,6-二氯-3-氟代苯基)乙醇,使其总收率由30%提高到了76%,而且缩短了时间,减少了污染,易于实施工业化生产.

海关参考信息

2902600000-乙苯
2903919090-氯苯
2905122000-异丙醇
2905143000-叔丁醇
💡 提示：海关信息按照顺序优先匹配，如需确认的海关信息，请参考相关资料。
详情请参考：📖 海关编码查询和海关进出口税则

专利信息

专利号:US-8785632-B2
优先权日:2004-08-26
标题:Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
发明人：CUI JINGRONG JEAN; FUNK LEE ANDREW; JIA LEI; KUNG PEI-PEI; MENG JERRY JIALUN; NAMBU MITCHELL DAVID; PAIRISH MASON ALAN; SHEN HONG; TRAN-DUBE MICHELLE
权利人:CUI JINGRONG JEAN; FUNK LEE ANDREW; JIA LEI; KUNG PEI-PEI; MENG JERRY JIALUN; NAMBU MITCHELL DAVID; PAIRISH MASON ALAN; SHEN HONG; TRAN-DUBE MICHELLE; AGOURON PHARMA; PFIZER
摘要:Enantiomerically pure compound of formula 1 n nare provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.