Synthesis in the R2 methyl analog 17b was achieved by reductive amination of your commercially accessible four trifluoromethoxyacetophenone 9b. Imidizolium ylide produced from Nbenzylimidazole employing diisopropylcarbamyl chloride and diisopropylethylamine was taken care of with trifluoromethoxybenzaldehyde in refluxing CH3CN to produce the carbamate, which upon hydrolysis afforded the benzylic alcohol . Ndebenzylation applying Pd/C followed by mesylation on the benzylic alcohol and subsequent response with amine 7 in THF during the presence of NaH at space temperature made the final merchandise like a mixture of diastereomers. The 3 alkyl derivatives have been all prepared in moderate yield by alkylation of amine 7, employing the corresponding bromides 15a?c, as illustrated in Scheme two.
Addition of ethyl and npropyl Grignard reagents to 4trifluoromethoxybenzaldehyde afforded screening library the corresponding benzylic alcohols despite the fact that 1 phenyl)butan1ol was prepared through the addition of nBuLi to trifluoromethoxybenzaldehyde. Alcohols 14a?c were converted to their corresponding bromides 15a?c) using PBr3 in ether and handled with amine in DMF inside the presence of K2CO3/KI at 90 ?C to provide the necessary compounds 17d?f being a mixture of diastereomers. Synthesis of carboxamide derivative 17g was achieved by nucleophilic addition of TMSCN to your imine formed amongst the amine 7 and 4trifluoromethoxybenzaldehyde at one hundred ?C and subsequent hydrolysis in ethanolic HCl. Response of 4 phenyl)oxirane 18 with 4trifluoromethoxybenzyl alcohol in presence of KOtBu at 60 ?C afforded alcohol 19. Additional oxidation with the ring opened merchandise, followed by removal on the pmethoxybenzyl group using TBDMSOTf afforded 2hydroxy1 phenyl)ethanone .
3Hydroxy1kinase phenyl)propan1one was synthesized from 13 in three methods involving a Reformatsky response with ethylbromoacetate in presence of Zn, LiAlH4 mediated reduction within the ester group to yield 21, and ultimately oxidation of your benzylic selleck chemical hif 1 inhibitors to alcohol employing MnO2 to supply the hydroxy ketone 22. Reductive amination of 20 and 22 with amine seven afforded nitroimidazooxazines 17h?i respectively. R3 modifications R3 modified nitroimidazooxazines were synthesized from the reductive amination of substituted trifluoromethoxybenzaldehydes with amine . Most of these aldehydes have been not offered commercially and have been synthesized as described in Schemes three, four and five. Consequently 2hydroxy4trifluoromethoxybenzoic acid 19 was put to use as being a critical intermediate from the synthesis of 2hydroxy bearing analogs plus the corresponding ether derivatives .
Esterification of with ethyl alcohol followed by alkylation with BnBr and cyclopropylmethylbromide gave the respective ether derivatives in terrific yields. Protection of phenolicOH group of 24 as its Omethoxymethyl ether was carried out making use of MOMCl/DIPEA to afford 27a.