【结 构 式】 |
【分子编号】25980 【品名】2-[4-[2-(heptylamino)ethyl]phenoxy]-2-methylpropionic acid 【CA登记号】 |
【 分 子 式 】C19H31NO3 【 分 子 量 】321.46008 【元素组成】C 70.99% H 9.72% N 4.36% O 14.93% |
合成路线1
该中间体在本合成路线中的序号:(X)The N-protection of 4-(2-aminoethyl)phenol (I) with benzyl chloroformate gives the N-benzyloxycarbonyl derivative (II), which is condensed with 1-methyl-1-(trichloromethyl)ethanol (III) by means of NaOH in acetone yielding the phenoxyisobutyric acid (IV). The deprotection of the amino group of (IV) by hydrogenation over Pd/C affords the ethylamino derivative (V), which is reprotected with 9-fluorenylmethoxycarbonyl protecting group to provide carbamate (VI). The acid group of (VI) is then coupled to a Sasrin polystyrene resin giving the N-protected resin (VII), which is deprotected with piperidine affording resin (VIII) with a free amino group, which is condensed with heptanoic acid (A) by means of DIC and HOBT to give the amide (IX). The reduction of the carbonyl group amide (IX) with BH3/THF yields the heptylamine (X), which is condensed with 4-fluorophenyl isocyanate (XI) to afford the urea (XII). Finally, this compound is treated with trifluoroacetic acid to eliminate the polystyrene resin and isolate the target compound. Alternatively, the heptylamine (X) can also be obtained directly by reductocondensation of the free amino group of the resin (VIII) with heptanal (B) by means of NaBH3CN.
【1】 Brown, P.J.; et al.; Generation of secondary alkyl amines on solid support by borane reduction. Application to the parallel synthesis of PPAR ligands. Synthesis 1997, 7, 778. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
13580 | 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate | 1885-14-9 | C7H5ClO2 | 详情 | 详情 | |
(B) | 25714 | octanal | 124-13-0 | C8H16O | 详情 | 详情 |
(A) | 35032 | heptanoic acid | 111-14-8 | C7H14O2 | 详情 | 详情 |
(I) | 19988 | 4-(2-Aminoethyl)phenol; Tyramine | 51-67-2 | C8H11NO | 详情 | 详情 |
(II) | 25974 | benzyl 4-hydroxyphenethylcarbamate | C16H17NO3 | 详情 | 详情 | |
(III) | 25975 | 1,1,1-trichloro-2-methyl-2-propanol | 57-15-8 | C4H7Cl3O | 详情 | 详情 |
(IV) | 25976 | 2-[4-(2-[[(benzyloxy)carbonyl]amino]ethyl)phenoxy]-2-methylpropionic acid | C20H23NO5 | 详情 | 详情 | |
(V) | 25977 | 2-[4-(2-aminoethyl)phenoxy]-2-methylpropionic acid | C12H17NO3 | 详情 | 详情 | |
(VI) | 25978 | 2-[4-(2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]ethyl)phenoxy]-2-methylpropionic acid | C27H27NO5 | 详情 | 详情 | |
(VII) | 25978 | 2-[4-(2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]ethyl)phenoxy]-2-methylpropionic acid | C27H27NO5 | 详情 | 详情 | |
(VIII) | 25977 | 2-[4-(2-aminoethyl)phenoxy]-2-methylpropionic acid | C12H17NO3 | 详情 | 详情 | |
(IX) | 25979 | 2-[4-[2-(heptanoylamino)ethyl]phenoxy]-2-methylpropionic acid | C19H29NO4 | 详情 | 详情 | |
(X) | 25980 | 2-[4-[2-(heptylamino)ethyl]phenoxy]-2-methylpropionic acid | C19H31NO3 | 详情 | 详情 | |
(XI) | 17977 | 1-Fluoro-4-isocyanatobenzene; 4-Fluorophenyl isocyanate | 1195-45-5 | C7H4FNO | 详情 | 详情 |
(XII) | 25981 | 2-(4-[2-[[(4-fluoroanilino)carbonyl](heptyl)amino]ethyl]phenoxy)-2-methylpropionic acid | C26H35FN2O4 | 详情 | 详情 |