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【结 构 式】

【药物名称】

【化学名称】N-[2-(4-Aminophenyl)-1(S)-[4-(2-fluoroethyl)piperidin-1-ylcarbonyl]ethyl]-4-[1(S)-benzyl-2-(4-morpholinyl)ethyl]pyridine-3-sulfonamide

【CA登记号】200270-65-1

【 分 子 式 】C34H45FN6O4S

【 分 子 量 】652.83795

【开发单位】Novartis (Originator)

【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Thrombin Inhibitors

合成路线1

Coupling of N-Boc-p-nitrophenylalanine (I) with 4-(2-fluoroethyl)piperidine (II) by means of 2-benzotriazolyl-1,1,3,3-tetramethyluronium tetrafluoborate (TBTU) gave amide (III) which, after acidic deprotection provided aminoamide (IV). 4-Chloropyridine-3-sulfonyl chloride (VI), generated from 4-hydroxy pyridine-3-sulfonic acid (V) by chlorination with PCl5/POCl3, was coupled with amine (IV) to afford sulfonamide (VII). Further condensation of (VII) with L-phenylalaninol (VIII) produced aminopyridine (IX). Conversion of the alcohol group of (IX) to the corresponding mesylate, followed by displacement with morpholine furnished the N-substituted morpholine (X). The nitro group of (X) was finally reduced to the target aniline by hydrogenation over Pd/C.

1 Ambler, J.; Baker E; Brown, L.; Butler, P.; Farr, D.; Dunnet, K.; Le Grand, D.; Janus, D.; Jones, D.; Menear, K.; Mercer, M.; Smith, G.; Talbot, M.; Tweed, M.; The discovery of orally available thrombin inhibitors: Studies towards the optimisation of CGH1668. Bioorg Med Chem Lett 1998, 8, 24, 3583.
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) 28516 (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-nitrophenyl)propionic acid C14H18N2O6 详情 详情
(II) 28517 4-(2-fluoroethyl)piperidine C7H14FN 详情 详情
(III) 28518 tert-butyl (1S)-2-[4-(2-fluoroethyl)-1-piperidinyl]-1-(4-nitrobenzyl)-2-oxoethylcarbamate C21H30FN3O5 详情 详情
(IV) 28519 (2S)-2-amino-1-[4-(2-fluoroethyl)-1-piperidinyl]-3-(4-nitrophenyl)-1-propanone C16H22FN3O3 详情 详情
(V) 28520 4-hydroxy-3-pyridinesulfonic acid C5H5NO4S 详情 详情
(VI) 28521 4-chloro-3-pyridinesulfonyl chloride C5H3Cl2NO2S 详情 详情
(VII) 28522 4-chloro-N-[(1S)-2-[4-(2-fluoroethyl)-1-piperidinyl]-1-(4-nitrobenzyl)-2-oxoethyl]-3-pyridinesulfonamide C21H24ClFN4O5S 详情 详情
(VIII) 28523 (2S)-2-amino-3-phenyl-1-propanol; L-phenylalanilol; (S)-2-amino-3-phenyl-1-propanol 5267-64-1 C9H13NO 详情 详情
(IX) 28524 4-[[(1S)-1-benzyl-2-hydroxyethyl]amino]-N-[(1S)-2-[4-(2-fluoroethyl)-1-piperidinyl]-1-(4-nitrobenzyl)-2-oxoethyl]-3-pyridinesulfonamide C30H36FN5O6S 详情 详情
(X) 28525 4-[[(1S)-1-benzyl-2-(4-morpholinyl)ethyl]amino]-N-[(1S)-2-[4-(2-fluoroethyl)-1-piperidinyl]-1-(4-nitrobenzyl)-2-oxoethyl]-3-pyridinesulfonamide C34H43FN6O6S 详情 详情
Extended Information