Benzofuran derivatives, their preparation method and their application in medicine
A phenyl compound technology, applied in the field of medicine, can solve problems such as hemorrhage and cerebral hemorrhage patients who cannot be used
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0435] (S)-6-(2-(((6-methoxy-2-(2-methylimidazo[2,1-b]thiazol-6-yl)benzofuran-4-yl)oxy )methyl)pyrrolidin-1-yl)nicotinonitrile 1
[0436]
[0437] first step
[0438] 1-(4-Hydroxy-6-methoxybenzofuran-2-yl)ethanone 1b
[0439] 1-(4-Benzyloxy-6-methoxybenzofuran-2-yl)ethanone 1a (2.1g, 7.1mmol, using the patent application "Example 203 on page 178 of the specification in WO2013163244" disclosed method prepared) was dissolved in 70mL of dichloromethane, cooled to -78°C, and pentamethylbenzene (7.1g, 47.9mmol) and boron trichloride in dichloromethane (1M, 10.3mL) were added to keep the Temperature reaction for 40 minutes. The reaction was quenched with saturated ammonium chloride (30 mL), extracted with ethyl acetate (80 mL×2), the organic phases were combined and dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography with eluent system C The residue gave the title compound 1b (1.4 g, yield: 96%).
[0440]...
Embodiment 2
[0462] (S)-6-(2-(((6-methoxy-2-(2-methoxyimidazo[2,1-b]thiazol-6-yl)benzofuran-4-yl)oxy Base) methyl) pyrrolidin-1-yl) nicotinonitrile 2
[0463]
[0464] Using the synthetic route of Example 1, replace the raw material 1i in the sixth step with 2-amino-5-methoxythiazole 2a (prepared by the method disclosed in the patent application "Example 244 on page 250 of the specification in WO2015052226") , The title compound 2 (3 mg) was obtained.
[0465] MS m / z(ESI):502.1[M+1]
[0466] 1 H NMR (400MHz, CDCl 3 ):δ8.48(s,1H),7.67(s,1H),7.64(d,1H),7.04(s,1H),6.95(s,1H),6.69(s,1H),6.48(d, 1H),6.45(s,1H),4.70(br,1H),4.33-4.27(m,2H),4.00(s,3H),3.87(s,3H),3.66(br,1H),3.47(br ,1H),2.32-2.17(m,4H).
Embodiment 3
[0468] 6-(6-methoxy-4-((2-(4-methoxyphenyl)thiazol-4-yl)methoxy)benzofuran-2-yl)-2-methylimidazo[ 2,1-b]thiazole 3
[0469]
[0470]
[0471] first step
[0472] (2-(4-Methoxyphenyl)thiazol-4-yl)methyl mesylate 3b
[0473] Dissolve (2-(4-methoxyphenyl)thiazol-4-yl)methanol 3a (2g, 9mmol, prepared by the method disclosed in the patent application "Example 323 on page 149 of the specification in WO2007107758") in Add triethylamine (913mg, 9mmol) to dichloromethane (20mL), cool to 0°C and stir, add dropwise methanesulfonyl chloride (1g, 9mmol) into the above reaction system, and react at 0°C for 3 hours. After the reaction was completed, the reaction was stopped, and 30 mL of water was added, extracted with dichloromethane (30 mL×3), the combined organic phases were dried over anhydrous sodium sulfate, and concentrated to obtain compound 3b, which was directly used in the next reaction without purification.
[0474] second step
[0475] 1-(6-methoxy-4-((2-(4-methoxyphen...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More