Preparation method of CSF-IR inhibitor
A reagent and catalyst technology, applied in the field of preparation of CSF-IR inhibitors, can solve the problems of unsuitability for industrial scale-up production, high preparation cycle and cost, insufficient substitution reaction yield, etc., to improve atom economy and reduce reaction difficulty. , the effect of shortening the synthesis cycle
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0047] In order to solve the above-mentioned technical problems, the first aspect of the present invention provides a preparation method of compound VII, which is characterized in that, comprising the following steps:
[0048] Step 3: Compound I is reacted with an organic amine under the action of a base to obtain Compound II;
[0049] Step 4: Compound II is demethylated and dearomatized to obtain Compound III;
[0050] Step 5: Compound III reacts with a methylating reagent under alkaline conditions to obtain Compound IV;
[0051] Step 6: Compound IV is reacted with a borate ester compound in the presence of a lithium reagent to obtain Compound V;
[0052] Step 7: Coupling reaction between compound V and compound VI to obtain VII;
[0053]
[0054] Among them, R 1 and R 2 identically or differently selected from hydrogen, C 1~6 saturated or unsaturated alkyl groups.
[0055] In some preferred embodiments, the R 1 and R 2 Respectively selected from hydrogen, isopropy...
Embodiment 1
[0120] Example 1, Preparation of Compound VI
[0121]
[0122] Compound VIII (100g, 760mmol), compound IX (174g, 836mmol), K 2 CO 3 (316g, 2280mmol) mixed with dioxane / water (1.2L) at a volume ratio of 5:1, replaced by argon, and added 3 ) 4 (10g), replaced by inert gas, and heated overnight at 90°C; after the reaction, filter, add water to the filtrate, extract with EA (2L×3), add anhydrous sodium sulfate to the combined organic phase to dry, filter, and concentrate the filtrate , the resulting crude product was purified by flash column chromatography (PE / EA=2:1) to obtain pure compound X (122 g, 90%).
[0123] Compound XI (99g, 423mmol) and K 2 CO 3 (39g, 282.2mmol) was dispersed in DMA (500mL), stirred at room temperature for 30min, compound X (50g, 282.2mmol) was added, and heated at 115°C overnight; after the reaction, cooled to room temperature, added H 2 O (1.5L), extracted with EA (3L×3), the organic phases were combined, washed with brine (3L), separated, ...
Embodiment 2
[0125] Example 2, Preparation of Compound VI
[0126]
[0127] Compound VIII (100g, 760mmol), compound IX (126.5g, 608mmol), K 2 CO 3 (210g, 1520mmol) mixed with dioxane / water (1L) with a volume ratio of 5:1, replaced with argon, and added Pd(PPh 3 ) 4 (8.2g), replaced by inert gas, and heated overnight at 90°C; after the reaction, filter, add water to the filtrate, extract with EA (2L×3), add anhydrous sodium sulfate to the combined organic phase, filter, concentrate The filtrate was purified by flash column chromatography (PE / EA=2:1) to obtain pure compound X (117 g, 87%).
[0128] Compound XI (66.3g, 282.2mmol) and K 2 CO 3 (31.2g, 225.76mmol) was dispersed in DMA (450mL), stirred at room temperature for 30min, compound X (50g, 282.2mmol) was added, and heated at 115°C overnight; after the reaction, cooled to room temperature, added H 2 O (1L), extracted with EA (3L×3), combined the organic phases, washed with brine (2.5L), separated the layers, added anhydrous...
PUM
Abstract
Description
Claims
Application Information
- R&D Engineer
- R&D Manager
- IP Professional
- Industry Leading Data Capabilities
- Powerful AI technology
- Patent DNA Extraction
Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.
© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com