Preparation method of erlotinib base monohydrate crystal form I
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology for erlotinib base and monohydrate, which is applied in the field of preparation of erlotinib base monohydrate crystal form Form I, can solve the problems of single solvent type, complicated operation, lack of extensiveness and the like, and achieves purity High, simple operation, safe and environmentally friendly process route
Active Publication Date: 2014-12-24
SHANDONG JINCHENG PHARMACEUTICAL GROUP CO LTD
View PDF4 Cites 2 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
[0008] Above-mentioned two all have more obvious defect, (1) method extraction, liquid separation, drying, the processing route of steaming solvent, industrialization process operation is complicated; Erlotinib base monohydrate crystal form Form I, the type of solvent used is single, not extensive
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0030] Add 10.0g of erlotinib hydrochloride, 0.93g of sodium hydroxide, and 60ml of methanol to a clean and dry 250ml reaction bottle, stir at room temperature for 0.5h, take 1.0ml of the reaction solution, add 0.5ml of water, and the reaction solution becomes clear to indicate the reaction After completion, the reaction solution was added dropwise to 120ml of water for 0.5h. After the dropwise addition was completed, under stirring, the temperature was lowered to 0-5°C, filtered with suction, and the filter cake was vacuum-dried at 20°C to obtain a white solid. 8.2 g, yield 89.5%, HPLC purity 99.8%.
Embodiment 2
[0032] Add 10.0g of erlotinib hydrochloride, 1.24g of sodium carbonate, 60ml of methanol to a clean and dry 250ml reaction bottle, stir at room temperature for 1.0h, take 1.0ml of the reaction solution, add 0.5ml of water, the reaction solution becomes clear, indicating that the reaction is complete , add the reaction solution dropwise to 240ml of water, and the dropping time is 0.5h. After the dropwise addition, under stirring, cool down to 0-5°C, filter with suction, and vacuum-dry the filter cake at 20°C to obtain a white solid, 8.3 g, yield 90.6%, HPLC purity 99.7%.
Embodiment 3
[0034] Add 10.0g of erlotinib hydrochloride, 1.4g of sodium hydroxide, and 30ml of dioxane to a clean and dry 250ml reaction bottle, stir at room temperature for 1.0h, take 1.0ml of the reaction solution, add 0.5ml of water, and the reaction solution becomes Clarify that the reaction is complete. Add the reaction solution dropwise to 60ml of water for 0.5h. After the dropwise addition, under stirring, cool down to 0-5°C, filter with suction, and dry the filter cake in vacuum at 50°C to obtain White solid, 8.1 g, yield 88.4%, HPLC purity 99.6%.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
PUM
Login to view more
Abstract
The invention belongs to the technical field of pharmaceutical chemicals, and in particular relates to a preparation method of an erlotinib base monohydrate crystal form I. The preparation method comprises the following steps: stirring and mixing erlotinib hydrochloride, base and an organic solvent, or stirring and mixing erlotinib base and an organic solvent; dropwise adding a solution system after an reaction or after being classified to water under a stirring condition; while stirring, decreasing temperature to 0-5 DEG; and filtering and drying in a vacuum environment to obtain erlotinib base monohydrate crystal form I. The erlotinib base monohydrate crystal form I is prepared by crystallization at room temperature through an organic solvent which is cheap, easy to prepare, green and environment-friendly; and the preparation method is safe and environment-friendly in process route, simple to operate, low in cost, good in repeatability, stable, applicable to industrial production and quite high in economic value. The prepared erlotinib base disclosed by the invention has high purity, and can be used for preparing erlotinib hydrochloride high in purity.
Description
technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a method for preparing erlotinib base monohydrate crystal form Form I. Background technique [0002] Erlotinib base, also known as Erlotinib, chemical name: 4-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine. Erlotinib base was listed in the United States in the form of hydrochloride in 2004. It is a reversible inhibitor of epidermal growth factor tyrosinase (EGFR) and is suitable for locally advanced and or metastatic non-small cell lung cancer. The structural formula is as follows: [0003] [0004] The patent US5747498 first disclosed the preparation method of erlotinib hydrochloride. The preparation method of erlotinib base mentioned in the patent is separated and purified by silica gel column, and the crystal form of erlotinib base is not mentioned in the patent. . [0005] At present, the disclosed process routes for...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/94
CPCC07D239/94
Inventor 伊茂聪孙滨马庆双南红燕
Owner SHANDONG JINCHENG PHARMACEUTICAL GROUP CO LTD
Login to view more 
Login to view more