A kind of benzidine compound and its application
A compound, benzidine technology, applied in the field of chemical medicine, can solve the problems of no good effect, unpublished druggability data, few structural types of RORγ inhibitors, etc., and achieve the effect of simple preparation method and suitable for large-scale industrial production
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Embodiment 1
[0055] This example provides a benzidine compound: N-(2'-fluoro-4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1 , 1'-biphenyl]-4-base)-2-(4-(methylsulfonyl)phenyl)acetamide, its preparation method comprises the steps:
[0056] (1) Preparation of 2-(4-amino-3-fluorophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol with the following structure:
[0057]
[0058] Difluoroaniline (6.0 g, 54 mmol), hexafluoroacetone trihydrate (12.5 g, 56.7 mmol) and p-toluenesulfonic acid (0.85 g, 5.4 mmol) were placed in a pressure vessel. After vacuuming, heat to 90°C with argon protection and react overnight. Cool to room temperature, wash once with saturated sodium bicarbonate, and extract three times with ethyl acetate (3×50 mL). The organic layers were combined, washed once with saturated sodium chloride, dried over anhydrous sodium sulfate, and the organic phase was spin-dried in vacuo. The crude product was separated through a silica gel column (PE:EA=10:1) to obtain 4.45 g of a white so...
Embodiment 2
[0074] This example provides a benzidine compound: 2-(4-(ethylsulfonyl)phenyl)-N-(2'-fluoro-4'-(1,1,1,3,3,3- Hexafluoro-2-hydroxypropane-2-yl)-[1,11,1'-biphenyl]-4-yl)acetamide, its preparation method comprises the steps:
[0075] Steps (1)-(4) are consistent with Example 1, and then step (5) is performed.
[0076] (5) Prepare 2-(4-(ethylsulfonyl)phenyl)-N-(2'-fluoro-4'-(1,1,1,3,3,3-hexafluoro- 2-Hydroxypropan-2-yl)-[1,11,1'-biphenyl]-4-yl)acetamide:
[0077]
[0078] Compound 2-(4-(ethylsulfonyl)phenyl)acetic acid (70.7 mg, 0.31 mmol), diisopropylethylamine (0.5 mL) and HATU (646.4 mg, 1.70 mmol) were dissolved in 20 mL of DCM. The reaction mixture was stirred at room temperature for 5 minutes, then the compound 2-(4'-amino-2-fluoro-[1,1'-biphenyl]-4-yl)-1,1,1,3,3 , 3-hexafluoro-2-propanol (100mg, 0.28mmol), and the resulting mixture was stirred at room temperature for 3 hours. The reaction was monitored by TLC. After the reaction was completed, water was added, extrac...
Embodiment 3
[0082] This example provides a benzidine compound: N-(2'-fluoro-4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1 , 1'-biphenyl]-4-base)-2-(4-nitrophenyl)acetamide, its preparation method comprises the steps:
[0083] Steps (1)-(4) are consistent with Example 1, and then step (5) is performed.
[0084] (5) Preparation of N-(2'-fluoro-4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1,1' - Biphenyl]-4-yl)-2-(4-nitrophenyl)acetamide:
[0085]
[0086] Compound 2-(4-nitrophenyl)acetic acid (56.2 mg, 0.31 mmol), diisopropylethylamine (0.5 mL) and HATU (646.4 mg, 1.70 mmol) were dissolved in 20 mL of DCM. The reaction mixture was stirred at room temperature for 5 minutes, then the compound 2-(4'-amino-2-fluoro-[1,1'-biphenyl]-4-yl)-1,1,1,3,3 , 3-hexafluoro-2-propanol (100mg, 0.28mmol), and the resulting mixture was stirred at room temperature for 3 hours. The reaction was monitored by TLC. After the reaction was completed, water was added, extracted with ethyl acetate (3×...
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