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【结 构 式】

【分子编号】26631

【品名】methyl 2-[5-[([2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]amino)carbonyl]-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate

【CA登记号】

【 分 子 式 】C30H30N4O6S

【 分 子 量 】574.65756

【元素组成】C 62.7% H 5.26% N 9.75% O 16.7% S 5.58%

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)

The reaction of N-tert-butylbenzenesulfonamide (I) with triisopropyl borate by means of BuLi in THF gives the boronic acid (II), which is condensed with 4-bromonitrobenzene (III) by means of palladium tetrakis(triphenylphosphine) to yield the N-tert-butyl-4'-nitrobiphenyl-2-sulfonamide (IV). The reduction of (IV) with H2 over Pd/C in methanol affords the biphenylamine (V), which is acylated with 3-(3-cyanophenyl)-5-(methoxycarbonylmethyl)-4,5-dihydroisoxazole-5-carboxylic acid (VI), by means of SOCl2 in acetonitrile affording the corresponding amide (VII). The reaction of (VII) with trifluoroacetic acid eliminates the tert-butyl protecting group providing intermediate (VIII). Finally, the cyano group of (VIII) is converted into amidino by reaction with HCl in chloroform/methanol and reaction of the intermediate imidate with ammonium acetate. Alternatively, biphenylamine (V) can also be obtained as follows: The reaction of 4-bromoaniline (IX) with tert-butoxycarbonyl anhydride in THF gives the corresponding carbamate (X), which is condensed with the boronic acid (II) by means of palladium tetrakis triphenylphosphine and deprotected with trifluoroacetic acid to afford the target intermediate (V).

1 Quan, M.L.; Wityak, J.; Galemmo, R.A. Jr.; Stouten, P.F.W.; Pruitt, J.R. (DuPont Pharmaceuticals Co.); Isoxazoline, isothiazoline and pyrazoline factor Xa inhibitors. EP 0874629; US 5939418; WO 9723212 .
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) 26626 N-(tert-butyl)benzenesulfonamide C10H15NO2S 详情 详情
(II) 26627 2-[(tert-butylamino)sulfonyl]phenylboronic acid C10H16BNO4S 详情 详情
(III) 26628 1-bromo-4-nitrobenzene 99-99-0 C6H4BrNO2 详情 详情
(IV) 26629 N-(tert-butyl)-4'-nitro[1,1'-biphenyl]-2-sulfonamide C16H18N2O4S 详情 详情
(V) 23363 4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide C16H20N2O2S 详情 详情
(VI) 26630 3-(3-cyanophenyl)-5-(2-methoxy-2-oxoethyl)-4,5-dihydro-5-isoxazolecarboxylic acid C14H12N2O5 详情 详情
(VII) 26631 methyl 2-[5-[([2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]amino)carbonyl]-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate C30H30N4O6S 详情 详情
(VIII) 26632 methyl 2-[5-([[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]amino]carbonyl)-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate C26H22N4O6S 详情 详情
(IX) 22531 4-Bromoaniline; 4-Bromophenylamine 106-40-1 C6H6BrN 详情 详情
(X) 26633 tert-butyl 4-bromophenylcarbamate C11H14BrNO2 详情 详情
Extended Information