【结 构 式】 |
【分子编号】58565 【品名】2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}phenyl)acetic acid 【CA登记号】 |
【 分 子 式 】C33H31ClF3NO3 【 分 子 量 】582.0619896 【元素组成】C 68.1% H 5.37% Cl 6.09% F 9.79% N 2.41% O 8.25% |
合成路线1
该中间体在本合成路线中的序号:(IX)The title compound was prepared by solid-phase synthesis on a Sasrin resin. The silylated m-hydroxyphenylacetic acid (I) was attached to the resin using DCC and DMAP to yield the acid-bound resin (II). The silyl group of (II) was then removed by treatment of resin (II) with tetrabutylammonium fluoride in THF. The resultant phenol (III) was coupled to 3-bromo-1-propanol (IV) under Mitsunobu conditions to afford the bromide functionalized resin (V). Displacement of the bromide ion of (V) with 2,2-diphenylethylamine (VI) furnished the secondary amine (VII), which was subjected to reductive alkylation with aldehyde (VIII) in the presence of NaBH(OAc)3 to produce the resin-bound product (IX). Cleavage from the solid support employing trifluoroacetic acid in CH2Cl2 provided the target carboxylic acid.
【1】 Collins, J.L.; et al.; Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem 2002, 45, 10, 1963. |
【2】 Willson, T.M.; Collins, J.L.; Maloney, P.R.; Fivush, A.M.; Stewart, E.L. (GlaxoSmithKline plc); Chemical cpds.. WO 0224632 . |
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),(II) | 58560 | 2-(3-{[tert-butyl(dimethyl)silyl]oxy}phenyl)acetic acid | C14H22O3Si | 详情 | 详情 | |
(III) | 58561 | 2-(3-hydroxyphenyl)acetic acid | C8H8O3 | 详情 | 详情 | |
(IV) | 12573 | 3-Bromo-1-propanol; 3-Bromopropanol | 627-18-9 | C3H7BrO | 详情 | 详情 |
(V) | 58562 | 2-[3-(3-bromopropoxy)phenyl]acetic acid | C11H13BrO3 | 详情 | 详情 | |
(VI) | 38962 | 2,2-diphenylethylamine; 2,2-diphenyl-1-ethanamine | 3963-62-0 | C14H15N | 详情 | 详情 |
(VII) | 58563 | 2-(3-{3-[(2,2-diphenylethyl)amino]propoxy}phenyl)acetic acid | C25H27NO3 | 详情 | 详情 | |
(VIII) | 58564 | 2-chloro-3-trifluoromethyl benzaldehyde | 93118-03-7 | C8H4ClF3O | 详情 | 详情 |
(IX) | 58565 | 2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}phenyl)acetic acid | C33H31ClF3NO3 | 详情 | 详情 |