Novel method for preparing thienopyrimidine compound and intermediate
A technology for compounds and mixtures, applied in the field of novel intermediates, can solve problems such as difficulty in purifying compounds, and achieve the effects of easy mass production and effective mass production
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0059] The preparation method according to the present disclosure includes step 1): obtaining the compound of formula 3 through the reaction between the compound of formula 4 and the compound of formula 5 in the presence of a base in an organic solvent.
[0060] In one embodiment, the compound of formula 3 may be (3-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[3,2-d]pyrimidine -4-yl)oxy)phenyl) tert-butyl carbamate or (3-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[3, 2-d]Pyrimidin-4-yl)oxy)phenyl)carbamate benzyl ester.
[0061] In one embodiment regarding step 1), in the presence of a base in an organic solvent, the compound 4-chloro-N-(4-(4-methylpiperazin-1-yl)phenyl)thieno [3,2-d]pyrimidin-2-amine is reacted with tert-butyl (3-hydroxyphenyl)carbamate, an example of a compound of formula 5 . Then, water or a mixed solvent of an organic solvent and water is added thereto for crystallization, and the product obtained is filtered to obtain (3-((2-((4-(4-methyl...
preparation Embodiment 1
[0165] Preparation Example 1. Preparation of (3-hydroxyphenyl) tert-butyl carbamate
[0166] 10 g (0.0916 mol) of 3-aminopentanol was dissolved in 500 ml of tetrahydrofuran, and 27 ml (0.119 mol) of di-tert-butyl dicarbonate was added thereto. The mixed solution was then stirred at a temperature of 25°C (room temperature) for 1 hour. After the reaction was completed, a mixed solvent of 25 ml of isopropanol and 50 ml of hexane was added to the residue to remove the solvent by distillation under reduced pressure, and the resulting solution was stirred for 2 hours. The resulting solid was filtered, washed with 50 ml of hexane, and dried at 40°C, whereby 17 g (yield: 90%) of tert-butyl (3-hydroxyphenyl)carbamate was obtained as the title compound as a white solid.
[0167] 1 H-NMR (300MHz, DMSO-d 6)δ9.25(s,1H),9.18(s,1H),7.01(m,1H),6.97(d,1H),6.83(dd,1H),6.34(m,1H),1.45(s,9H )
preparation Embodiment 2
[0168] Preparation Example 2. Preparation of 4-chloro-N-(4-(4-methylpiperazin-1-yl)phenyl)thieno[3,2-d]pyrimidin-2-amine
[0169] Dissolve 150g (0.44mol) of 2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[3,2-d]pyrimidin-4(3H)-one in 600ml of acetonitrile While raising the reaction temperature to 75°C, 124ml of phosphorus oxychloride (POCl 3 ) diluted in 150ml of acetonitrile solution. The mixed solution was then stirred at a temperature of 75° C. for 1 hour. After the reaction was completed, the reaction temperature was cooled to 25°C, and 1.5 liters of cooling water at a temperature of 0°C to 4°C was slowly added to the reaction solution. Then, an aqueous solution prepared by dissolving 263 g of sodium hydroxide in 750 ml of water was added to the reaction solution while maintaining the reaction temperature at 20° C. or lower, and the resulting reaction solution was stirred at a temperature of 25° C. for 1 hour . The resulting solid was filtered, washed with 1.5 liters...
PUM
| Property | Measurement | Unit |
|---|---|---|
| wavelength | aaaaa | aaaaa |
| melting point | aaaaa | aaaaa |
| melting point | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More