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【结 构 式】

【分子编号】34825

【品名】methyl 2-[5-[([5-[2-(aminosulfonyl)phenyl]-2-pyrimidinyl]amino)carbonyl]-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate

【CA登记号】

【 分 子 式 】C24H20N6O6S

【 分 子 量 】520.52564

【元素组成】C 55.38% H 3.87% N 16.15% O 18.44% S 6.16%

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:(XI)

3-Cyanobenzaldehyde (I) was converted to oxime (II) by reaction with hydroxylamine in pyridine. The intermediate nitrile oxide, generated from chlorination and further elimination of HCl, underwent a [2+3] cycloaddition with itaconic acid monomethyl ester (III) to produce the isoxazoline (IV). The carboxylate group of (IV) was then activated as the corresponding acid chloride (V) upon treatment with SOCl2. Boronic acid (VII) was prepared from N-tert-butyl benzenesulfonamide (VI) by lithiation with n-butyllithium, followed by reaction with triisopropyl borate and quenching with HCl. Subsequent Suzuki coupling of (VII) with 2-amino-5-bromopyrimidine (VIII) using Pd(PPh3)4 and Na2CO3 afforded the 2-amino-4-arylpyrimidine (IX). Condensation of amine (IX) with acid chloride (V) in the presence of Et3N gave amide (X). The N-tert-butyl group of (X) was then deprotected by means of trifluoroacetic acid to yield (XI) as the trifluoroacetate salt. The cyano group of (XI) was converted to imidate (XII) with HCl and MeOH. This was finally reacted with ammonium acetate in MeOH to furnish the title amidine.

1 Quan, M.L.; Liauw, A.Y.; Ellis, C.D.; et al.; Design and synthesis of isoxazoline derivatives as factor Xa inhibitors. 1. J Med Chem 1999, 42, 15, 2752.
2 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) 13245 3-Formylbenzonitrile; 3-Cyanobenzaldehyde 24964-64-5 C8H5NO 详情 详情
(II) 23357 3-[(hydroxyimino)methyl]benzonitrile C8H6N2O 详情 详情
(III) 34820 2-(2-methoxy-2-oxoethyl)acrylic acid 7338-27-4 C6H8O4 详情 详情
(IV) 26630 3-(3-cyanophenyl)-5-(2-methoxy-2-oxoethyl)-4,5-dihydro-5-isoxazolecarboxylic acid C14H12N2O5 详情 详情
(V) 34821 methyl 2-[5-(chlorocarbonyl)-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate C14H11ClN2O4 详情 详情
(VI) 26626 N-(tert-butyl)benzenesulfonamide C10H15NO2S 详情 详情
(VII) 26627 2-[(tert-butylamino)sulfonyl]phenylboronic acid C10H16BNO4S 详情 详情
(VIII) 34822 5-bromo-2-pyrimidinamine; 5-bromo-2-pyrimidinylamine 7752-82-1 C4H4BrN3 详情 详情
(IX) 34823 2-(2-amino-5-pyrimidinyl)-N-(tert-butyl)benzenesulfonamide C14H18N4O2S 详情 详情
(X) 34824 methyl 2-[5-[[(5-[2-[(tert-butylamino)sulfonyl]phenyl]-2-pyrimidinyl)amino]carbonyl]-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate C28H28N6O6S 详情 详情
(XI) 34825 methyl 2-[5-[([5-[2-(aminosulfonyl)phenyl]-2-pyrimidinyl]amino)carbonyl]-3-(3-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetate C24H20N6O6S 详情 详情
(XII) 34826 methyl 2-(5-[([5-[2-(aminosulfonyl)phenyl]-2-pyrimidinyl]amino)carbonyl]-3-[3-[imino(methoxy)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetate C25H24N6O7S 详情 详情
Extended Information