• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】45838

【品名】[1-[4-[[3,4-bis(difluoromethoxy)phenyl](chloro)methyl]phenyl]-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methyl 2-(trimethylsilyl)ethyl ether; (2-[[1-[4-[[3,4-bis(difluoromethoxy)phenyl](chloro)methyl]phenyl]-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methoxy]ethyl)(trimethyl)silane

【CA登记号】

【 分 子 式 】C24H25ClF10O4Si

【 分 子 量 】630.982332

【元素组成】C 45.68% H 3.99% Cl 5.62% F 30.11% O 10.14% Si 4.45%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

Metallation of 1,4-dibromobenzene (I) followed by addition to hexafluoroacetone afforded the bis(trifluoromethyl)carbinol (II), which was subsequently protected as the trimethylsilylethoxymethyl ether (III). 3,4-Dihydroxybenzaldehyde (IV) was alkylated with either chlorodifluoromethane or methyl chlorodifluoroacetate to give the bis(difluoromethyl)ether (V). Addition of either the organolithium or Grignard reagent prepared from aryl bromide (III) to aldehyde (V) furnished the diaryl carbinol (VI), which was converted to chloride (VII) by treatment with SOCl2 and diisopropyl ethylamine. Selective carbomethoxylation of 3,4-dimethylpyridine (VIII) using dimethyl carbonate and LDA afforded (IX). Condensation of chloride (VII) with the lithium anion of (IX) yielded the triarylpropionate derivative (X). Ester group hydrolysis with LiOH, followed by acidification with NH4Cl, provided the decarboxylated compound (XI). After SEM group cleavage by treatment with tetrabutylammonium fluoride, the pyridine ring of the resulting (XII) was finally oxidized to the target N-oxide.

2 Guay, D.; Ducharme, Y.; Blouin, M.; Hamel, P.; Girard, M. (Merck Frosst Canada Inc.); Tri-aryl ethane derivs. as PDE IV inhibitors. EP 0873311; JP 2000501742; US 5710170; WO 9722586 .
1 Brideau, C.; Ducharme, Y.; Blouin, M.; et al.; Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PB-12.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 18983 1,4-dibromobenzene 106-37-6 C6H4Br2 详情 详情
(II) 45834 2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol C9H5BrF6O 详情 详情
(III) 45835 [1-(4-bromophenyl)-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methyl 2-(trimethylsilyl)ethyl ether; (2-[[1-(4-bromophenyl)-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methoxy]ethyl)(trimethyl)silane C15H19BrF6O2Si 详情 详情
(IV) 39749 3,4-dihydroxybenzaldehyde 139-85-5 C7H6O3 详情 详情
(V) 45836 3,4-bis(difluoromethoxy)benzaldehyde C9H6F4O3 详情 详情
(VI) 45837 [3,4-bis(difluoromethoxy)phenyl][4-(2,2,2-trifluoro-1-(trifluoromethyl)-1-[[2-(trimethylsilyl)ethoxy]methoxy]ethyl)phenyl]methanol 597-43-3 C24H26F10O5Si 详情 详情
(VII) 45838 [1-[4-[[3,4-bis(difluoromethoxy)phenyl](chloro)methyl]phenyl]-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methyl 2-(trimethylsilyl)ethyl ether; (2-[[1-[4-[[3,4-bis(difluoromethoxy)phenyl](chloro)methyl]phenyl]-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methoxy]ethyl)(trimethyl)silane C24H25ClF10O4Si 详情 详情
(VIII) 39869 3,4-dimethylpyridine 583-58-4 C7H9N 详情 详情
(IX) 45839 methyl 2-(3-methyl-4-pyridinyl)acetate C9H11NO2 详情 详情
(X) 45840 methyl 3-[3,4-bis(difluoromethoxy)phenyl]-2-(3-methyl-4-pyridinyl)-3-[4-(2,2,2-trifluoro-1-(trifluoromethyl)-1-[[2-(trimethylsilyl)ethoxy]methoxy]ethyl)phenyl]propanoate C33H35F10NO6Si 详情 详情
(XI) 45841 4-[2-[3,4-bis(difluoromethoxy)phenyl]-2-[4-(2,2,2-trifluoro-1-(trifluoromethyl)-1-[[2-(trimethylsilyl)ethoxy]methoxy]ethyl)phenyl]ethyl]-3-methylpyridine; [1-[4-[1-[3,4-bis(difluoromethoxy)phenyl]-2-(3-methyl-4-pyridinyl)ethyl]phenyl]-2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]methyl 2-(trimethylsilyl)ethyl ether C31H33F10NO4Si 详情 详情
(XII) 45842 2-[4-[1-[3,4-bis(difluoromethoxy)phenyl]-2-(3-methyl-4-pyridinyl)ethyl]phenyl]-1,1,1,3,3,3-hexafluoro-2-propanol C25H19F10NO3 详情 详情
Extended Information