Pyrimidine-2,4-diamines and Their Uses
a technology of diamine and pyrimidine, which is applied in the field of diaryl pyrimidine2, 4diamines, can solve the problems of low selectivity of potent inhibitors that have been discovered, and achieve the high selectivity that would be required
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Benefits of technology
Problems solved by technology
Method used
Image
Examples
example 1
Synthesis of N2-Chlorocarbonyl-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine
[0119]
[0120] To pale yellow stirring mixture of N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine (2.5 g, 5.31 mmol) and triphosgene (1.67 g, 5.62 mmol) in dicholoroethane (20 mL) at 0 0C, NEt3 (1.08 g, 1.5 mL, 10.76 mmol) in dichloroethane (10 mL) was added dropwise under nitrogen atmosphere for 10 min. The orange reaction mixture was allowed to stir for 15 min at 0 0C followed by refluxing at 90 0C overnight. The heterogeneous tan orange reaction mixture was cooled to room temperature. The reaction mixture was diluted with EtOAc (75 mL). Precipitated white solid formed was filtered. The white solid was collected, treated with water, filtered and dried to provide N2-chlorocarbonyl-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidine...
example 2
Synthesis of N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[[2-(morpholin-4-yl)ethoxy]carbonyl]-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine
[0122]
[0123] N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[[2-(morpholin-4-yl)ethoxy]carbonyl]-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine was prepared from 4-(2-hydroxyethyl)morpholine and N2-chlorocarbonyl-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine. The crude solid, obtained after concentration of the reaction mixture followed by treatment with aq. NaHCO3, was purified by NEt3 treated silica gel column chromatography. 1H NMR (CDCl3): δ 10.32 (s, 2H), 8.89 (s, 1H), 8.18 (d, 1H, J=2.9 Hz), 7.49 (d, 1H, J=8.8 Hz), 7.06 (d, 1H, J=8.8 Hz), 6.52 (s, 2H), 4.29 (m, 2H), 3.81 (s, 3H), 3.74 (s, 6H), 3.57 (m, 4H), 2.56 (m, 2H), 2.33 (m, 4H), 1.48 (s, 6H). LCMS: ret. time: 8.30 min.; purity: 92%; MS (m / e): 628 (MH+).
example 3
Synthesis of 4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[[1-methyl-piperidin-2-yl)methoxy]carbonyl]-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine
[0124]
[0125] 4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[[1-methyl-piperidin-2-yl)methoxy]carbonyl]-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine was prepared from N2-chlorocarbonyl-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine and 1-methyl-2-piperidinemethanol in the similar manner as described in the general procedure. The crude off white solid obtained after the general workup was subjected to HPLC purification. 1H NMR (DMSO-d6): δ 11.03 (s, 1H), 9.67 (s, 1H), 8.33 (d, 1H, J=3.0 Hz), 7.41 (d, 1H, J=8.5 Hz), 7.17 (d, 1H, J=8.5 Hz), 6.56 (s, 2H), 4.10 (d, 2H, J=4.7 Hz), 3.80 (s, 6H), 3.64 (s, 3H), 2.70-2.66 (m, 1H), 2.09 (s, 3H), 1.97-1.92 (m, 2H), 1.58-1.07 (m, 12H). LCMS: ret. time: 8.54 min.; purity: 92%; MS (m / e): 627 (MH+)...
PUM
Property | Measurement | Unit |
---|---|---|
Fraction | aaaaa | aaaaa |
Fraction | aaaaa | aaaaa |
Fraction | aaaaa | aaaaa |
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