新产品编号:641219
Chemical Name: N-[4-Cyano-3-(trifluoromethyl)phenyl]-2(R)-hydroxy-2-methyl-3-[4-(isothiocyanato)phenylsulfanyl]propionamide
CAS No. 247090-55-7, 247090-62-6 (S)
项目整合开发状态: Biological Testing
项目研究机构: University of Tennessee, Memphis (Originator)
合成路线:Coupling of the chiral auxiliary (R)-proline (I) with methacryloyl chloride (II) under Schotten-Baumann conditions provided amide (III).This was converted to bromolactone (IV) by asymmetric bromolactonization in the presence of N-bromosuccinimide.Subsequent acid hydrolysis yielded the chiral (R)-bromoacid (V),that was converted to acid chloride (VI) and then coupled with 4-amino-2-trifluoromethylbenzonitrile (VII) in DMA at low temperature to afford anilide (VIII).Coupling with 4-aminothiophenol (IX) using NaH in THF produced sulfide (X).Finally,conversion of the aniline precursor (X) to the target isothiocyanate was achieved by reaction with thiophosgene in the presence of NaHCO3.
📌 参考资料/链接：
参考文献标题:Chiral nonsteroidal affinity ligands for the androgen receptor.1.Bicalutamide analogues bearing electrophilic groups in the B aromatic ring
文献作者:Kirkovsky,L.; Mukherjee,A.; Yin,D.; Dalton,J.T.; Miller,D.D.
参考来源:J Med Chem 2000,43(4),581
📄 详细内容
合成路线:Coupling of the chiral auxiliary (R)-proline (I) with methacryloyl chloride (II) under Schotten-Baumann conditions provided amide (III).This was converted to bromolactone (IV) by asymmetric bromolactonization in the presence of N-bromosuccinimide.Subsequent acid hydrolysis yielded the chiral (R)-bromoacid (V),that was converted to acid chloride (VI) and then coupled with 4-amino-2-trifluoromethylbenzonitrile (VII) in DMA at low temperature to afford anilide (VIII).Coupling with 4-aminothiophenol (IX) using NaH in THF produced sulfide (X).Finally,conversion of the aniline precursor (X) to the target isothiocyanate was achieved by reaction with thiophosgene in the presence of NaHCO3.
参考文献标题:Affinity labeling of the androgen receptor with nosteroidal chemoaffinity ligands
文献作者:Mukherjee,A.; Kirkovsky,L.I.; Kimura,Y.; Marvel,M.M.; Miller,D.D.; Dalton,J.T.
参考来源:Biochem Pharmacol 1999,58(8),1259