Irreversible inhibitors of tyrosine kinases
A technology of CH2 and compounds, applied in the field of irreversible inhibitors of tyrosine kinases, can solve problems such as not very effective
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0426] N-[4-(3-Bromo-phenylamino)-pyrido[4,3-d]pyrimidin-7-yl]-N-(3-morpholin-4-ylpropyl)-acrylamide
[0427] General method A:
[0428] 7-Amino-4-[(3-bromophenyl)amino]-pyrido[4,3-d]pyrimidine can be acylated according to methods known to those skilled in the art [J Med Chem, 1995:3780] , giving N-[4-(3-bromo-phenylamino)-pyrido[4,3-d]pyrimidin-7-yl]-N-(3-morpholin-4-ylpropyl)-propene amides. For example, acylation with acrylic acid can be achieved by using standard condensation reagents such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (EDAC) or by using acryloyl chloride and a tertiary base For example, diisopropylethylamine is realized as an acid scavenger.
[0429] Then, the N-alkylation reaction of -acrylamide can be achieved by methods known to those skilled in the art. For example, treatment with standard reagents such as sodium hydride converts the amide to its monoanion, followed by treatment with an appropriate halide such as N-(3-chloropropyl)morpholine...
Embodiment 2
[0433] N-[4-(3-Bromo-phenylamino)-pyrido[3,4-d]pyrimidin-6-yl]-N-(3-morpholin-4-ylpropyl)-acrylamide
[0434] 4-[(3-bromo-phenyl)amino]-6-[(3-morpholinopropyl)amino]pyrido[3,4-d]pyrimidine (400mg, 0.90mmol) (from 4-[(3-bromo-phenyl)amino]-6-fluoropyrido[3,4-d]pyrimidine and 3-morpholinopropan-1-ylamine), DMAP (40mg) and Et 3 To the solution of N (excess, 2.0 mL) was added acryloyl chloride (1.2 molar equivalents, 1.08 mmol, 89 μL). After stirring for 1 hour, two more portions of acid chloride (89 μL each) were added over 2 hours and the reaction mixture was stirred at 20° C. for 1 hour, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and chromatographed on silica gel using methanol / ethyl acetate (1:9) to methanol / ethyl acetate (1:5) as The eluate gave N-[4-(3-bromo-phenylamino)-pyrido[3,4-d]pyrimidin-6-yl]-N-(3-morpholinopropyl)-acrylamide (1...
Embodiment 3
[0441] N-[4-(3-Bromo-phenylamino)-quinazolin-7-yl]-acrylamide
[0442] Anhydrous dimethylformamide (DMF, 5.0 mL) was added to an ice-cooled solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) (0.288 g). After stirring for 5 minutes, the mixture became a solution and the ice bath was removed. The reaction mixture was stirred for an additional 3 hours at room temperature. Then, the reaction mixture was poured into a mixture of ice and water, and made basic by adding saturated sodium bicarbonate solution. This aqueous mixture was extracted three times with ethyl acetate, and the combined extracts were dried over magnesium sulfate. The solution was filtered and concentrated in vacuo to give a pale yellow solid. The solid was dissolved in 100 mL of methanol, filtered, and concentrated in vacuo to approximately 10 mL. The solid precipitated from the solution was collected and dried under vacuum at 80 °C to give 50 mg of N-[4-(3-bromo-phenylamino)-quin...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More - R&D
- Intellectual Property
- Life Sciences
- Materials
- Tech Scout
- Unparalleled Data Quality
- Higher Quality Content
- 60% Fewer Hallucinations
Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.
© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com