cas 179688-26-7, Ethyl 4,5-bis(2-methoxyethoxy)-2-nitrobenzoate

Articles about 179688-26-7Total 25 be found

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Synthetic method of erlotinib
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.
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(2020/07/12)

Synthesis and evaluation of novel 18F-labeled quinazoline derivatives with low lipophilicity for tumor PET imaging
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.
Chong, Yan,Chang, Jin,Zhao, Wenwen,He, Yong,Li, Yuqiao,Zhang, Huabei,Qi, Chuanmin
p. 42 - 53
(2018/02/06)

Method for synthesizing erlotinib intermediate with microchannel reactor
The invention discloses a method for synthesizing an erlotinib intermediate with a microchannel reactor, belongs to the field of synthesis of anti-tumor drugs in organic synthesis and solves the problems of low yield, poor purity, high energy consumption,
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Paragraph 0048-0050; 0060; 0070; 0080; 0089-0093; 0101; 0132

(2018/09/08)

A method for preparing environmental protection of erlotinib hydrochloride
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.
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(2017/09/26)

Preparation method of 4,-5-bis(2-methoxyl ethyoxyl)-2-ethyl nitrobenzoate
The invention relates to a preparation method of 4,-5-bis(2-methoxyl ethyoxyl)-2-ethyl nitrobenzoate. The preparation method comprises the following steps: (1) enabling 4,5-dihydroxy ethyl benzoate to react with a protective agent, then reacting with nitr
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Paragraph 0027

(2017/08/31)

Erlotinib hydrochloride key intermediate preparation method
The present invention relates to an erlotinib hydrochloride key intermediate preparation method, particularly to a method for high reaction rate, high purity and high yield preparation of 2-nitro-4,5-bis(2-methoxyethoxy) ethyl benzoate from 3,4-bis(methoxyethoxy)ethyl benzoate, wherein in the presence of a catalytic amount of concentrated sulfuric acid, 3,4-bis(methoxyethoxy)ethyl benzoate and concentrated sulfuric acid are subjected to a reaction by using acetic acid and acetic anhydride as a solvent. According to the present invention, the method has characteristics of mild reaction condition, rapid reaction rate, high conversion rate, high product purity, safety and environmental protection, and is suitable for industrial production.
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Paragraph 0023; 0024; 0025; 0026; 0027; 0028; 0029

(2017/08/30)

Preparation method of erlotinib intermediate
The invention belongs to the field of chemical synthesis and relates to a preparation method of an erlotinib intermediate 6,7-di(methoxyethoxy)quinazoline-4-one. According to the invention, by screening reaction conditions, a preparation technology of the
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Paragraph 0020-0027

(2018/03/01)

Model quinazoline chlorethazine compound and its preparation method and application for treating tumor (by machine translation)
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.
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(2016/10/07)

Quinazoline derivatives
no abstract published
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(2016/08/23)

Erlotinid hydrochloride method for the preparation of key intermediate
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.
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Paragraph 0063; 0064

(2016/11/09)

FUSED QUINAZOLINE DERIVATIVES AND USES THEREOF
Fused quinazoline derivatives and uses thereof as protein tyrosine kinase inhibitors and aurora kinase inhibitors are disclosed. Said protein tyrosine kinase inhibitors and aurora kinase inhibitors can be used in treating cancers, leukaemia and the diseases relevant to differentiation and proliferation. Said protein tyrosine kinase and aurora kinase dual inhibitors are the compounds represented by the following general formula or salts thereof.
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(2013/05/23)

Design and synthesis of novel quinazoline nitrogen mustard derivatives as potential therapeutic agents for cancer
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.
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)

Isolation of highly pure erlotinib hydrochloride by recrystallization after nucleophilic substitution of an impurity with piperazine
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 %.
Zhang, Gengzhen,Zha, Linlin
p. 2303 - 2309
(2013/07/26)

POLYCYCLIC QUINAZOLINES, PREPARATION THEREOF, AND USE THEREOF
At least one active pharmaceutical ingredient is chosen from polycyclic quinazolines of formula V, pharmaceutically acceptable salts thereof, and hydrates of the pharmaceutically acceptable salts. The active pharmaceutical ingredients disclosed may be inhibitors of protein tyrosine kinase inhibitors and/or aurora kinase. The active pharmaceutical ingredients can be used for treating cancers susceptible to treatment with protein tyrosine kinase inhibitors and/or aurora kinase inhibitors.
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(2011/12/12)

Method of Synthesizing 6,7-Substituted 4-Anilino Quinazoline
A method of synthesizing 6,7-substituted 4-anilino quinazoline employs 3,4-substituted benzoic acid as an initial reactant, and the 6,7-substituted 4-anilino quinazoline is obtained by an esterifying step, a nitrating step, a reducing step, a cyclizing step, and an one-pot reaction. In the above method, the initial reactant has low cost and yield. of the 6,7-substituted 4-anilino quinazoline is high, therefore, production cost can be reduced effectively, and competitive power of the product of the 6,7-substituted 4-anilino quinazoline can be improved.
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Page/Page column 6

(2010/11/03)

QUINAZOLINE DERIVATIVES AS RAF KINASE MODULATORS AND METHODS OF USE THEREOF
Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O)t; Ra is O or S.
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Page/Page column 174

(2009/10/22)

THERAPEUTIC OXY-PHENYL-ARYL COMPOUNDS AND THEIR USE
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.
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Page/Page column 183

(2009/05/28)

Syntheses of 4-(indole-3-yl)quinazolines - A new class of epidermal growth factor receptor tyrosine kinase inhibitors
The epidermal growth factor (EGF) family of membrane receptors has been identified as a key element in the complex signaling network that is utilized by various classes of cell-surface receptors. The synthesis and pharmacological results of 4-(indole-3-yl)quinazolines are described. The synthesized compounds are new high potent EGFR-tyrosine kinase inhibitors with excellent cytotoxic properties at different cell lines. Furthermore the 4-(indole-3-yl)quinazolines show some tendencies to inhibit the HER-2 TK, too. Moreover this substance class has remarkable strong fluorescence properties.
Lueth, Anja,Loewe, Werner
p. 1478 - 1488
(2008/09/21)

Improved synthesis of substituted 6,7-dihydroxy-4-quinazolineamines: Tandutinib, erlotinib and gefitinib
The synthesis of three substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib (1), erlotinib (2) and gefitinib (3) in improved yields is reported. The intermediates were characterized by NMR and the purities determined by HPLC.
Knesl, Petr,Roeseling, Dirk,Jordis, Ulrich
p. 286 - 297
(2007/10/03)

PROCESS FOR PRODUCING 6,7-BIS(2-METHOXYETHOXY)-QUINAZOLIN-4-ONE
A process comprising a reaction of ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate with a formic acid compound in the presence of an ammonium carboxylate gives 6,7-bis(2-methoxyethoxy)quinazolin-4-one in a high yield.
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Page/Page column 6-7

(2008/06/13)

COMPOUND INHIBITING IN VIVO PHOSPHORUS TRANSPORT AND MEDICINE CONTAINING THE SAME
An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and ---- represents a single bond or a double bond, R5 represents optionally substituted aryl or the like, Z represents - N=CHR6R7 or the like, R6 and R7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R101 and R102 together form =O, and R103 and R104 represent H, or R101 and R104 together from a bond, and R102 and R103 together form a bond.
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Page/Page column 194

(2010/11/08)

Fluorine-18 labeling of 6,7-disubstituted anilinoquinazoline derivatives for positron emission tomography (PET) imaging of tyrosine kinase receptors: Synthesis of18F-Iressa and related molecular probes
Inhibitors of tyrosine kinase enzymatic activity represent a promising new class of antineoplastic agents. Although clinical studies performed over the last decade give more insight on the potential therapeutic applications of such drugs, identification of the individual patients who might benefit from them remains a major challenge. We have developed a synthetic strategy for the production of a wide variety of radiolabeled 6,7-disubstituted 4-anilinoquinazolines suitable for noninvasive imaging of tyrosine kinase receptors to predict therapy effectiveness. Three new F-18 labeled radiopharmaceuticals based on the therapeutic agents Tarceva, Iressa, and ZD6474 were synthesized. Decay-corrected yields varied between 25 and 40% for a total synthesis time of 120 min, thus providing F-18 labeled tyrosine kinase inhibitors in quantities and times practical for use as PET radiopharmaceuticals. Copyright
Seimbille, Yann,Phelps, Michael E.,Czernin, Johannes,Silverman, Daniel H. S.
p. 829 - 843
(2007/10/03)

Quinazoline derivatives
The invention relates to certain 4-(substitutedphenylamino)quinazoline derivatives of formula (I), their produgs and pharmaceutically acceptable salts wherein R1, R2, R3, R4, m and n are described in said formula. The compounds of formula (1), their produgs and pharmaceutically acceptable salts are useful for the treatment of hyperproliferative diseases.
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(2008/06/13)

ALKYNYL AND AZIDO-SUBSTITUTED 4-ANILINOQUINAZOLINES
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(2008/06/13)

Aniline derivatives
The invention concerns aniline derivatives of formula I STR1 wherein m is 1, 2 or 3, n is 0, 1, 2 or 3, Q is phenyl or naphthyl or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, and X, R1 and R2 are defined in the claims; or pharmaceutical compositions containing them, and the methods of using the compounds as tyrosine kinase inhibitors and for the treatment of proliferative diseases such as cancer.
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(2008/06/13)