- Industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles-catalyzed hydrogenation of nitroarenes
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The development of green and efficient methods for hydrogenation of nitroarenes is still highly demanding in organic synthesis. Herein, we report an industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles process for the synthesis of aryl amines with good yields via hydrogenation of nitroarenes. Nine key anti-cancer drug intermediates were successfully achieved with protocol. And Osimertinib intermediate 4m can be smoothly synthesized at a 2.67 kg-scale with >99.5% HPLC purity. This protocol features cheap carbon source, highly catalytic activity, simple operation, kilogram-scalable and recyclable catalysts (eight times without observable losing activity).
- Fu, Lihua,Li, Dingzhong,Lu, Hao,Qiu, Renhua,Sun, Tulai,Xing, Chen,Yang, Tianbao
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- A high-purity of gefitinib preparation method
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The invention relates to a process for preparing high-purity of gefitinib method the method comprises the following 5 steps: 1st step exotic fragrance orchid [...], 2nd step etherification, 3rd step nitration, step reduction 4th, 5th step ring gathers passes through purification of the final product is obtained. The programme raw material sources are extensive, the cost is reduced, improving the quality of products, it is easy to further popularization and application.
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Paragraph 0020-0021
(2019/04/04)
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- Efficient preparation method of gefitinib
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The invention provides an efficient preparation method of gefitinib. 2-nitro-4,5-dimethoxybenzonitrile is used as a starting material and subjected to a demethylation reaction, a substitution reaction, a nitro reduction reaction, a ring forming reaction, an amino substitution reaction and the like to obtain a finished gefitinib product. By means of the preparation method, gefitinib with the purityhigher than 99.9% can be obtained, the total yield of the preparation method is 61-75%, raw materials used in the method are low in price, there are only five steps in the process route, the operation is simple and easy to control, the yield of the target product is high, and the repeatability is good.
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- New synthesis method of gefitinib
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The invention relates to a new synthetic method of an anti-tumor drug 4-(3-chloro-4-fluorophenylamino)-7-methoxy-6-(3-morpholinylpropoxy)quinazoline (gefitinib, I). According to the synthesis method,synthesis is performed through a novel synthetic intermediate. Before a quinazoline mother ring is synthesized, hydroxy of 3-hydroxy-4-methoxybenzonitrile is reacted with 3-morpholinopropyl chloride firstly, so that the steps of adding protecting groups and removing the protecting groups are reduced, the synthesis route is shortened, the step number of synthesis is lowered, raw materials are cheapand easily obtained, the use of chlorinated reagents which heavily pollute the environment is avoided, the purification process is simplified, the pH (potential of hydrogen) value does not need to berepeatedly adjusted, the operation is safe and simple, and the reaction yield exceeds 60%.
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Paragraph 0008; 0018
(2018/04/02)
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- Design, synthesis, and antitumor activity of novel quinazoline derivatives
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In an attempt to explore a new class of epidermal growth factor receptor (EGFR) inhibitors, novel 4-stilbenylamino quinazoline derivatives were synthesized through a Dimorth rearrangement reaction and characterized via IR, 1H-NMR, 13C-NMR, and HRMS. Methoxyl, methyl, halogen, and trifluoromethyl groups on stilbeneamino were detected. These synthesized compounds were evaluated for antitumor activity in vitro against eight human tumor cell lines with an MTS assay. Most synthesized compounds exhibited more potent activity (IC50 = ~2.0 μM) than gefitinib (IC50 > 10.0 μM) against the A431, A549, and BGC-823 cell lines. Docking methodology of compound 6c and 6i binding into the ATP site of EGFR was carried out. The results showed that fluorine and trifluoromethyl played an important role in efficient cell activity.
- Wang, Liuchang,Li, Pengna,Li, Baolin,Wang, Yawen,Li, Jiangtao,Song, Limei
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- Synthetic method of 4-(3-chlorine-4-fluorophenyl)-7-methoxyl-6-[3-(4-morpholinyl) propoxy] quinazoline
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The invention discloses a synthetic method of 4-(3-chlorine-4-fluorophenyl)-7-methoxyl-6-[3-(4-morpholinyl) propoxy] quinazoline. The synthetic method comprises the following steps that 3-hydroxy-4-methoxy benzonitrile serves as the raw material and reacts with 3-chloropropyl morpholine, and 4-methoxyl-3-[3-(4-morpholinyl) propoxy] cyanobenzene is obtained; the 4-methoxyl-3-[3-(4-morpholinyl) propoxy] cyanobenzene is nitrified with mixed acid, and 2-nitryl-4-methoxyl-5-[3-(4-morpholinyl) propoxy] cyanobenzene is obtained; the 2-nitryl-4-methoxyl-5-[3-(4-morpholinyl) propoxy] cyanobenzene is subjected to reduction, and then 2-amino-4-methoxyl-5-[3-(4-morpholinyl) propoxy] cyanobenzene is obtained; 3-chlorine-4-fluoroaniline reacts with an imine complex, N'-(3-chlorine-4-phenyl)-N, N-dimethyl formamidine is obtained, and the imine complex is prepared from DMF and dimethyl sulfate through heating and a reaction; 2-amino-4-methoxyl-5-[3-(4-morpholinyl) propoxy] cyanobenzene reacts with the N'-(3-chlorine-4-fluorophenyl)-N, N-dimethyl formamidine, so that the 4-(3-chlorine-4-fluorophenyl)-7-methoxyl-6-[3-(4-morpholinyl) propoxy] quinazoline is obtained. The synthetic method has the advantages of being environmentally friendly and high in yield.
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Paragraph 0053; 0054; 0055
(2016/10/10)
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- Convergent approach for commercial synthesis of gefitinib and erlotinib
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An efficient, economical and large-scale convergent synthesis of epidermal growth factor receptor- tyrosine kinase inhibitors gefitinib (1, Iressa) and erlotinib (2, Tarceva) approved by U.S. FDA for the treatment of non-small-cell lung cancer is described. The formation of 4-anilinoquinazolines are achieved in a simple one-pot reaction of suitable forniamidine intermediates and substituted anilines involving Dimroth rearrangement, thereby avoiding the need to make quinazolin-4(3H)-one intermediates, which require a large experimental inputs. Using this process, we have produced drug candidates 1 with overall yield of 66% from 4-methoxy-5-[3-(4-morpholinyl) propoxy]-2-nitrobenzonitrile (3) and 2 with 63% from 4-bis(2-methoxyethoxy)-2-nitrobenzonitrile (6) on a multigram scale.
- Chandregowda, Venkateshappa,Rao, Gudapati Venkateswara,Reddy, Goukanapalli Chandrasekara
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p. 813 - 816
(2012/12/30)
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- Synthesis of [11C]Iressa as a new potential PET cancer imaging agent for epidermal growth factor receptor tyrosine kinase
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Iressa (Gefitinib) is an orally active inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK) involved in cell signal transduction processes critical to proliferation, apoptosis, repair, and angiogenesis of cancer cells. [11C]Iressa was first designed and synthesized as a new potential positron emission tomography (PET) cancer imaging agent for EGFR-TK in 30-40% radiochemical yield with 4.0-6.0 Ci/μmol specific activity at end of bombardment (EOB).
- Wang, Ji-Quan,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
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p. 4102 - 4106
(2007/10/03)
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- PROCESS FOR THE MANUFACTURE OF GEFITINIB
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The invention relates to a process for the manufacture of 4-(3'-chloro-4'- fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline which comprises the rearrangement reaction optionally in the presence of a suitable catalyst of 3-(3'-chloro-4'-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)-3,4-dihydroquinazolin- 4-imine of Formula (II).
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Page/Page column 18
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF 4-(3'-CHLORO-4'-FLUOROANILINO)-7-METHOXY-6-(3-MORPHOLINOPROPOXY) QUINAZOLINE
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The invention relates to chemical processes and intermediates useful in the manufacture of the quinazoline derivative 4 (3'' chloro 4'' fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline. In particular, the invention relates to processes for the manufacture of 7-methoxy-6-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one of Formula (II) and 4-methoxy-5-(3-morpholinopropoxy)-2-nitrobenzonitrile of Formula (III) and their use in the manufacture of said quinazoline derivative
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