Substituted triazine phenyl urea derivatives and application thereof
A technology of substituents and compounds, which is applied in the field of substituted triazine phenylurea derivatives and their uses, and can solve problems such as ineffectiveness
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0135] Example 1: Compound 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(4-(4-hydroxypiperidin-1-yl)-6-methyl-1 , 3,5-triazinyl-2-amino)-4-methylphenyl)urea (HSCA-001) synthesis
[0136] Synthetic route 1
[0137]
[0138] step one:
[0139]
[0140] 1a (3.69g, 20mmol) was dissolved in 20mL of anhydrous THF, and methylmagnesium bromide in ether (8mL, 24mmol, 3M) was slowly added into it by syringe at -20°C. After the dropwise addition was completed, it was raised to room temperature, and the solvent was concentrated under reduced pressure. Add 20 mL of saturated ammonium chloride solution to the residue, extract the solution with ethyl acetate (20 mL×2), wash the organic phase with 30 mL of brine, combine the organic layers, dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure. 3.2 g of solid was obtained, ie product 1b, yield 97%. MS[M+1] + 165.2.
[0141] Step two:
[0142]
[0143] 1c (1.11g, 5mmol), 1d (837mg, 5.5mmo...
Embodiment 2
[0153] Example 2: Compound 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-methyl-3-(4-methyl-6-morpholinyl-1,3, Synthesis of 5-Triazinyl-2-amino)phenyl)urea (HSCA-002)
[0154] Synthetic route 2
[0155]
[0156] 1 g (150 mg, 0.319 mmol) and morpholine (1 mL) were added to 10 mL of ethanol solution, and stirred at room temperature for 3 hours. After concentrating the solvent under reduced pressure, water was added, extracted with ethyl acetate, and the organic phase was collected and concentrated. Purification on preparative silica gel plates afforded 60 mg of 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-methyl-3-(4-methyl-6-morpholinyl-1, 3,5-Triazinyl-2-amino)phenyl)urea (HSCA-002), yield 36%. 1 H NMR (400MHz, DMSO-d 6 )δppm: 9.07(s, 1H), 8.76(s, 1H), 8.72(s, 1H), 8.14(s, 1H), 7.80(s, 1H), 7.59(m, 2H), 7.10(m, 1H ), 7.03(m, 1H), 3.68(m, 4H), 3.58(m, 4H), 2.20(s, 3H), 2.15(s, 3H); MS[M+1] + 522.0.
[0157] With the method of embodiment 1 and 2 can obtain following compo...
Embodiment 3
[0213] Example 3: Compound 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-methyl-3-(4-methyl-6-morpholinyl-1,3, Synthesis of 5-Triazinyl-2-oxo)phenyl)urea (HSCA-003)
[0214] Synthetic route 3
[0215]
[0216] step one:
[0217]
[0218] 3a (1.3 g, 7.9 mmol) and diisopropylethylamine (1.6 g, 15.8 mmol) were dissolved in 15 mL of DMF, to which morpholine (620 mg, 0.71 mmol) was added at -5°C. After stirring at the same temperature for 2 hours, water was added to the reaction liquid, extracted with ethyl acetate, and the organic phase was collected, dried over anhydrous sodium sulfate, and filtered. The solvent was concentrated under reduced pressure to obtain 1.4 g of crude product 3b, which was directly used in the next reaction.
[0219] Step two:
[0220]
[0221] Compound 3c (544mg, 3.55mmol) was dissolved in 15mL DMF, cooled to -5°C and sodium hydride (142mg, 3.55mmol) was added into the solution. At the same temperature, after stirring for 30 minutes, 0.7 g of c...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More