TX-525

Chemical Name: 17alpha-Acetoxy-6alpha-methyl-19-nor-1beta,2beta-dihydrocyclopropa[1,2]pregn-4-ene-3,20-dione
CAS No. 193087-98-8
项目整合开发状态: Preclinical
项目研究机构: Th閞amex (Originator)
合成路线:The title compound was prepared by two related ways.Reduction of pregn-4-ene (I) with sodium dithionite provided pregnane (II) with 5a-H configuration.Then,dehydrogenation with Pd(OAc)2 in refluxing acetonitrile gave pregn-1-ene (III).Cyclopropanation of (III) with dimethylsulfoxonium methylide (generated from trimethylsulfoxonium iodide and NaH in DMSO),yielded (IV).This was brominated with pyridinium tribromide,and the resulting 4-bromo compound (V) was dehydrobrominated by treatment with Li2CO3 and LiBr in DMF at 140 C to give the target compound.Alternatively,(I) was hydrogenated in the presence of Pd(OH)2 to afford pregnane (VI) with 5b-H configuration.The sequence of bromination with pyridinium tribromide,and elimination of the resulting bromide (VII) with Li2CO3 and LiBr provided pregn-1-ene (VIII),which was reduced to alcohol (IX) with NaBH4 in the presence of CeCl3 at 0 C.Insertion of carbene by means of a Simmons-Smith reaction with CH2I2 and Et2Zn yielded cyclopropane derivative (X),and this was again oxidized to ketone (XI) with Jones' reagent in acetone.Finally,the sequence of bromination and dehydro-bromination as before provided the target 4,5-unsaturated ketone.