Background and overview of preparation and application of indole-7-boronic acid
Indole-7-boronic acid is a boronic acid derivative. Boric acid derivatives are widely used in organic synthesis for the formation of carbon-carbon bonds. In the Suzuki coupling, aryl halides and aryl or vinyl borates or boronic acids are coupled using Pd(PPh3)4.
Preparation and application of indole-7-boronic acid
In a flask protected from light, KH (62 mg, 1.53 mmol) was suspended in anhydrous THF (0.4 ml) at 0°C under an argon atmosphere. 7-bromoindole (300 mg, 1.53 mmol) in anhydrous THF (2.6 ml) was added and the mixture was stirred for 15 minutes. After cooling to -78°C, a solution of tert-butyllithium in pentane (3.1 mmol) which had been previously cooled to -78°C was added dropwise. The mixture was allowed to reach room temperature and stirred for 15 minutes and cooled again to -78°C. Add B(OMe)3 (341μl, 1.53mmol) and continue stirring at room temperature for 3 hours. H2O (5ml) was added and the mixture was extracted with EtAcO (2x10ml). The aqueous phase was acidified to pH 1 with 10% HCl and extracted again with EtAcO (3×10 ml). The combined organic extracts were dried over anhydrous MgSO and filtered. The calcium carbonate evaporates the solvent, leaving crude indole-7-boronic acid as a light brown oil. 1HNMR(MHz,Chloroform-d)δ9.52(s,1H),8.03(dd,J＝7.1,1.2Hz,1H),7.98- 7.92(m,1H),7.43( dd, J＝3.2, 2.2Hz, 1H), 7.33 (dd, J＝7.8, 7.0Hz, 1H), 6.68 (dd, J＝3.3, 2.0Hz, 1H).
Preparation and application of indole-7-boronic acid
Indole-7-boronic acid can be used to prepare 2-amino-7,8-dihydro-6H-potassium trifluoroborate quinazolin-5-one oxime derivatives with the following structure. This compound is an Hsp90 inhibitor. The chaperone heat shock protein (Hsp90) is an emerging target in cancer therapy due to its important role in regulating key proteins in cell growth, survival, and differentiation pathways. Hsp90 inhibitors also have medical applications in the treatment of viral infections and inflammatory disease states.
References
[1] [Invented in China, authorized by China] CN201280056411.1 EP1 receptor ligand
[2] [China invention, China invention authorization] CN200880023140.3 Quinazoline-oxime derivatives used as Hsp90 inhibitors
