Preparation method of piperazidine derivatives containing indolyl-3-carboxylic acid skeleton and application of piperazidine derivatives in anticancer drugs
A derivative, piperazine technology, applied in the field of medicinal chemistry, can solve the problems of lack of localization of tumor tissue, damage to normal cells, and reduced efficacy, and achieve the effects of strong repeatability, mild experimental environment and good stability.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment approach
[0023] A detailed embodiment of the present invention is as follows:
[0024] Step 1: Under stirring at 0°C, compound 1 was dissolved in anhydrous methanol, and SOCl was added dropwise 2 , transferred to 80°C, stirred and reacted, the solvent was removed under reduced pressure, extracted with ethyl acetate, the organic layer was washed successively with saturated brine and distilled water, dried over anhydrous magnesium sulfate, and the solvent was removed under pressure to obtain intermediate compound 2.
[0025] Step 2: Under stirring at 0°C, sequentially add the THF solution dissolved in the intermediate compound 2 into the reaction vessel, then slowly dropwise add the THF solution dissolved in a small amount of NaH, move to room temperature, and slowly add the halogenated hydrocarbon dropwise. Continue to stir the reaction for 12h, remove THF under reduced pressure, extract with ethyl acetate, wash the organic layer with saturated brine and distilled water successively, dr...
Embodiment 1
[0029] Example 1: Preparation of 1-ethyl-indole-3-formyl-(4-sulfonamide)piperazine (compound 7)
[0030]
[0031] Under stirring at 55°C, intermediate 4, HOBt, anhydrous dichloromethane, and EDC were sequentially added to the reaction vessel, and intermediate 6 was added after 30±5 min. Continue to stir, follow the reaction by TLC, after 8±3h, the reaction solution is successively mixed with saturated KHSO 4 Aqueous solution, saturated Na 2 CO 3 , washed with saturated brine, distilled under reduced pressure, the obtained solid crude product was dissolved in absolute ethanol and recrystallized to obtain the target compound.
[0032] white solid, yield 63%; 1 H NMR (DMSO-d 6 , 300MHz)δ: 7.75(t, J=3.00Hz, 3H, ArH, CHN), 7.71(s, 1H, ArH), 7.68(t, J=5.60Hz, 2H, ArH), 7.63(t, J= 5.40Hz, 1H, ArH), 7.47 (d, J=6.20Hz, 1H, ArH), 7.21 (t, J=5.70Hz, 1H, ArH), 7.11 (t, J=5.60Hz, 1H, ArH), 3.79(s, 3H, CH 3 ), 3.71(t, J=3.70Hz, 4H, CH 2 ), 2.96(t, J=3.70Hz, 4H, CH 2 ).ESI-MS: m / ...
Embodiment 2
[0033] Example 2: Preparation of 1-methyl-indole-3-formyl-(4-sulfonamide) piperazine (compound 8)
[0034]
[0035] For the preparation method, refer to Example 1. white solid, yield 67%; 1 H NMR (DMSO-d 6 , 300MHz) δ: 7.88 (dd, J=5.00Hz, J=1.50Hz, 2H, ArH, CHN), 7.72 (s, 1H, ArH), 7.69 (t, J=1.60Hz, 1H, ArH), 7.67 (t, J=1.70Hz, 1H, ArH), 7.64 (d, J=5.90Hz, 1H, ArH), 7.48 (d, J=6.20Hz, 1H, ArH), 7.21 (t, J=5.80Hz, 1H, ArH), 7.11 (t, J=5.70Hz, 1H, ArH), 3.80 (s, 3H, CH 3 ), 3.71(t, J=3.60Hz, 4H, CH 2 ), 2.98(t, J=3.60Hz, 4H, CH 2 ).ESI-MS: m / z 464.3 (M + ).
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More