183322-16-9Relevant articles and documents
Synthetic method of erlotinib
-
Paragraph 0040-0042; 0043-0044, (2020/07/12)
The invention relates to a synthetic method of erlotinib, and belongs to the technical field of chemical synthesis. The preparation method comprises the following synthesis steps: (1) reacting a compound I with 2-chloroethyl methyl ether to generate a compound II; (2) oxidizing the compound II through peracetic acid to generate a compound III; (3) reacting the compound III with benzene sulfonyl chloride to generate a compound IV; (4) carrying out a ring closing reaction on the compound IV, ammonium chloride and formamide to generate a compound V; (5) reacting the compound V with phosphorus oxychloride to generate a compound VI; and (6) reacting the compound VI with m-aminophenylacetylene to generate a compound VII erlotinib. The invention provides a new synthetic route, and the used raw materials are common materials, are simple and easily available, can adapt to production of various scales, and the synthetic method has good industrial production prospects.
Synthesis and evaluation of novel 18F-labeled quinazoline derivatives with low lipophilicity for tumor PET imaging
Chong, Yan,Chang, Jin,Zhao, Wenwen,He, Yong,Li, Yuqiao,Zhang, Huabei,Qi, Chuanmin
, p. 42 - 53 (2018/02/06)
Four novel 18F-labeled quinazoline derivatives with low lipophilicity, [18F]4-(2-fluoroethoxy)-6,7-dimethoxyquinazoline ([18F]I), [18F]4-(3-((4-(2-fluoroethoxy)-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine ([18F]II), [18F]4-(2-fluoroethoxy)-7-methoxy-6-(2-methoxyethoxy)quinazoline ([18F]III), and [18F]4-(2-fluoroethoxy)-6,7-bis(2-methoxyethoxy)quinazoline ([18F]IV), were synthesized via a 2-step radiosynthesis procedure with an overall radiochemical yield of 10% to 38% (without decay correction) and radiochemical purities of >98%. The lipophilicity and stability of labeled compounds were tested in vitro. The log P values of the 4 radiotracers ranged from 0.52 to 1.07. We then performed ELISA to measure their affinities to EGFR-TK; ELISA assay results indicated that each inhibitor was specifically bounded to EGFR-TK in a dose-dependent manner. The EGFR-TK autophosphorylation IC50 values of [18F]I, [18F]II, [18F]III, and [18F]IV were 7.732, 0.4698, 0.1174, and 0.1176?μM, respectively. All labeled compounds were evaluated via cellular uptake and blocking studies in HepG2 cell lines in vitro. Cellular uptake and blocking experiment results indicated that [18F]I and [18F]III had excellent cellular uptake at 120-minute postinjection in HepG2 carcinoma cells (51.80?±?3.42%ID/mg protein and 27.31?±?1.94%ID/mg protein, respectively). Additionally, biodistribution experiments in S180 tumor-bearing mice in vivo indicated that [18F]I had a very fast clearance in blood and a relatively high uptake ratio of tumor to blood (4.76) and tumor to muscle (1.82) at 60-minute postinjection. [18F]III had a quick clearance in plasma, and its highest uptake ratio of tumor to muscle was 2.55 at 15-minute postinjection. These experimental results and experiences were valuable for the further exploration of novel radiotracers of quinazoline derivatives.
Preparation method of 3,4-di(2-methoxyl ethoxyl) ethyl benzoate
-
Paragraph 0029; 0030, (2017/07/19)
The invention belongs to the field of drug synthesis and relates to a preparation method of an anticancer drug intermediate, and in particular to a preparation method of 3,4-di(2-methoxyl ethoxyl) ethyl benzoate. The formula is as shown in the description. The preparation method is researched and reported in many literatures or patents, but organic solvents such as acetonitrile, acetone and DMF are needed to take part in. According to the preparation method provided by the invention, the solvents in the existing literatures or patents are not needed, but a product which is high in yield and purity can be obtained. The preparation method is a green and environmental-friendly preparation method and is suitable for industrial production.
A method for preparing environmental protection of erlotinib hydrochloride
-
Paragraph 0069-0071, (2017/09/26)
The invention discloses an environment-friendly method for preparing high-yield erlotinib hydrochloride. The method comprises the following steps: directly performing cyclic condensation by taking 2-amino-4,5-di(2-methoxy ethyoxyl) ethyl benzoate hydrochloride as a key intermediate, reacting with aminophenylacetylene to generate erlotinib hydrochloride after performing chlorination, and refining to obtain the high-purity erlotinib hydrochloride. The process route provided by the invention is mild in reaction condition and high in yield; the first-class reagent and other reagents harmful to the environment and the operators are not used, the byproduct is few, the aftertreatment is simple and the commercial process can be easily processed.
Quinazoline derivatives
-
Paragraph 0125, (2016/08/23)
no abstract published
Model quinazoline chlorethazine compound and its preparation method and application for treating tumor (by machine translation)
-
Paragraph 0106; 0107; 0108, (2016/10/07)
A novel quinazoline nitrogen mustard compound is characterized in that: one end is provided with a nitrogen mustard alkylating group; the other end is provided with a 6, 7-substituted quinazoline structure; a substituent R1 is located at a site 4 of a quinazoline matrix, and represents 2-, 3-, 4- nitrogen mustard substituent; and substituents R2, R3 are located at site 6 and 7 of a quinazoline matrix, and represent methoxyethoxy, methoxy, morpholine propoxy, 3-etrahydrofuran oxygen group and hydroxyl group. The compound has a structure shown as a formula A. Experiments show that the compound can cause cross-linking of DNA, and is a bifunctional alkylating agent. In vivo antitumor activity experiment show that the compound has good activity; furthermore, the compound has the advantage of low toxicity, which a nitrogen mustard drug is lack of. At the same time, the compound is easy for synthesis, has high total yield. Advantages of the compound show that it has great potential to become a drug for treatment of cancer.
Erlotinid hydrochloride method for the preparation of key intermediate
-
Paragraph 0058; 0059, (2016/11/09)
The invention discloses a preparation method of an erlotinib hydrochloride key intermediate 4-chloro-6,7-di(2-methoxyethoxy)quinazoline, which comprises the following steps: reacting the raw material ethyl 3,4-dihydroxybenzoate with ethyl 2-methoxysulfonate, nitrating, reducing, cyclizing and chlorinating to obtain the key intermediate 4-chloro-6,7-di(2-methoxyethoxy)quinazoline. The method has the advantages of mild reaction conditions, low cost, high purity and high total yield (up to 74.8%), and can easily implement industrial production.
A Mild and Regioselective Route to Functionalized Quinazolines
Maiden, Tracy M. M.,Swanson, Stephen,Procopiou, Panayiotis A.,Harrity, Joseph P. A.
supporting information, p. 14342 - 14346 (2015/10/05)
A Rh-catalyzed ortho-amidation cyclocondensation sequence gave a range of 4-aminoquinazolines in high yield. The method features a remarkably mild C(sp2)-H activation step and can be exploited to rapidly access compounds with established biological activity.
Design and synthesis of novel quinazoline nitrogen mustard derivatives as potential therapeutic agents for cancer
Li, Shilei,Wang, Xiao,He, Yong,Zhao, Mingxia,Chen, Yurong,Xu, Jingli,Feng, Man,Chang, Jin,Ning, Hongyu,Qi, Chuanmin
, p. 293 - 301 (2013/10/01)
Thirteen novel quinazoline nitrogen mustard derivatives were designed, synthesized and evaluated for their anticancer activities in vitro and in vivo. Cytotoxicity assays were carried out in five cancer cell lines (HepG2, SH-SY5Y, DU145, MCF-7 and A549) and one normal human cell line (GES-1), in which compound 22b showed very low IC50 to HepG2 (the IC50 value is 3.06 μM), which was lower than Sorafenib. Compound 22b could inhibit cell cycle at S and G2/M phase and induce cell apoptosis. In the HepG2 xenograft model, 22b exhibited significant cancer growth inhibition with low host toxicity in vivo.
Isolation of highly pure erlotinib hydrochloride by recrystallization after nucleophilic substitution of an impurity with piperazine
Zhang, Gengzhen,Zha, Linlin
, p. 2303 - 2309 (2013/07/26)
Optimized synthesis and purification of erlotinib hydrochloride (N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazoline-4-amine hydrochloride) were studied. Highly polar piperazine was used in a nucleophilic substitution reaction with the chlorinated intermediate byproduct N-(3-ethynylphenyl)-6(2- chloroethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride. As a result, N-(3-ethynylphenyl)-6(2-chloroethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride was completely transformed to N-(3-ethynylphenyl)-6(2- piperzinoethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride. The polarity of N-(3-ethynylphenyl)-6(2-piperzinoethoxy)-7-(2-methoxyethoxy) quinazolin-4-amine hydrochloride was changed, and its molecule was enlarged. It was easy to remove this larger, more polar, compound by recrystallization. Highly pure erlotinib hydrochloride was obtained with low impurity content (99.9 %.
