179688-27-8

Basic information

• Product Name: Ethyl 4,5-bis(2-methoxyethoxy)-2-aminobenzoate
• Synonyms: 2-Amino-4,5-bis(2-methoxyethoxy)benzoic acid ester;2-Amino-4,5-bis(2-methoxyethoxy)benzoic acid ethyl ester;4,5-Bis(2-methoxyethoxy)anthranilic acid ethyl ester;Ethyl 4,5-bis(2-methoxyethoxy)-2-aminobenzoate;Methyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate;Ethyl 2-aMino-4,5-bis(2-Methoxyethoxy)benzoate;Erlotinib interMidiate IV;Benzoic acid,2-aMino-4,5-bis(2-Methoxyethoxy)-, ethyl ester
• CAS NO: 179688-27-8
• Molecular Formula: C15H23NO6
• Molecular Weight: 313.35
• EINECS: 1592732-453-0
• Product Categories: intermidiate of Erlotinib hydrochloride;Erlotinib INTERMEDIATES
• Mol File: 179688-27-8.mol

Chemical Properties

• Boiling Point: 456.4 °C at 760 mmHg
• Flash Point: 183.9 °C
• Appearance: /
• Density: 1.148
• Vapor Pressure: 1.62E-08mmHg at 25°C
• Refractive Index: 1.514
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 2.52±0.10(Predicted)
• CAS DataBase Reference: Ethyl 4,5-bis(2-methoxyethoxy)-2-aminobenzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 4,5-bis(2-methoxyethoxy)-2-aminobenzoate(179688-27-8)
• EPA Substance Registry System: Ethyl 4,5-bis(2-methoxyethoxy)-2-aminobenzoate(179688-27-8)

Safety Data

• Hazardous Substances Data: 179688-27-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl 4,5-bis(2-methoxyethoxy)-2-aminobenzoate is used as an intermediate in the synthesis of Erlotinib for its role as a selective EGFR-tyrosine kinase inhibitor and antineoplastic agent. This makes it a crucial component in the development of cancer treatments, particularly for solid tumors.

InChI:InChI=1/C15H23NO6/c1-4-20-15(17)11-9-13(21-7-5-18-2)14(10-12(11)16)22-8-6-19-3/h9-10H,4-8,16H2,1-3H3

Upstream product

• 179688-26-7 2-nitro-4,5-bis(2-methoxyethoxy)benzoic acid ethyl ester 
• 3943-89-3 Ethyl protocatechuate 
• 183322-16-9 3,4-bis(2-methoxyethoxy)benzoic acid ethyl ester 
• 819813-71-3 3,4-bis(2-methoxyethoxy)-benzoic acid 

Downstream Products

• 179688-29-0 6,7-bis(2-methoxyethoxy)-3,4-dihydroquinazolin-4-one 
• 183322-18-1 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline 
• 183319-69-9 erlotinib hydrochloride 
• 214471-57-5 N'-[2-carbethoxy-4,5-bis(2-methoxyethoxy)phenyl]-N,N-dimethylformamidine 
• 773071-69-5 2-(3-chloromethylbenzoylamino)-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester 
• 1351125-29-5 C₂₆H₂₇ClFNO₇ 
• 1351125-31-9 C₂₅H₂₇ClN₂O₇ 
• 1351125-34-2 C₂₇H₂₈FN₃O₆ 
• 1351124-92-9 2-hydroxy-4,5-bis(2-methoxy-ethoxy)benzoic acid 
• 179688-29-0 6,7-bis-(2-methoxyethoxy)-4(3H)quinazolinone 
• 1456621-40-1 N¹-(6,7-bis(2-methoxyethoxy)quinazolin-4-yl)-N²,N²-bis(2-chloroethyl)benzene-1,2-diamine hydrochloride 
• 1447828-82-1 N¹-(6,7-bis(2-methoxyethoxy)quinazolin-4-yl)-N³,N³-bis(2-chloroethyl)benzene-1,3-diamine hydrochloride 
• 214484-83-0 4-[(3-dimethylaminophenyl)amino]-5,6-bis(2-methoxyethoxy)-3-quinolinecarbonitrile 

Relevant articles and documents

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.

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.

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,

An efficient method for reduction of nitroaromatic compounds to the corresponding aromatic amines with NH2NH2·H2O catalysed by H2O2-treated activated carbon

An efficient and green protocol for the reduction of nitroaromatic compounds to the corresponding amines has been developed. The reduction catalyst system includes NH2NH2·H2O and H2O2-treated activated carbon. Without adding additional metals, the H2O2-treated activated carbon could be reused for many cycles without decreasing catalytic efficiency. The aromatic amines could be obtained in good to excellent yields.

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

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.

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.

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.

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 %.

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.