• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】19289

【品名】tert-butyl 2-[[1-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-4-piperidinyl]oxy]acetate

【CA登记号】

【 分 子 式 】C22H32N2O6

【 分 子 量 】420.50596

【元素组成】C 62.84% H 7.67% N 6.66% O 22.83%

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:(XIV)

2) The reaction of 4-hydroxypiperidine (VII) with benzyl chloroformate (VIII) by means of triethylamine in dichloromethane gives the expected benzyloxycarbonyl derivative (IX), which is condensed with tert-butyl 2-bromoacetate (X) by means of tetrabutylammonium bisulfate and NaOH, yielding 2-[1-(benzyloxycarbonyl)piperidin-4-yloxy]acetic acid tert-butyl ester (XI). The deprotection of (XI) as ususal affords 2-(4-piperidinyloxy)acetic acid tert-butyl ester (XII), which is condensed with N-(benzyloxycarbonyl)-L-alanine (XIII) by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methyl-morpholine (NMM) in dichloromethane to yield the acylated piperidine (XIV). The deprotection of (XIV) as usual affords compound (XV), which is acylated at the free amino group with 4-cyanobenzoyl chloride (V) and tetrabutylammonium bisulfate to give 2-[1-[N-(4-cyanobenzoyl)-L-alanyl]piperidin-4-yloxy]acetic acid tert-butyl ester (XVI). The reaction of the cyano group of (XVI) with hydroxylamine affords compound (XVII) with a hydroxyamidino substituent. Finally, the tert-butyl ester group of (XVII) is converted in ethyl ester by hydrolysis with hot fomic acid to the corresponding acetic acid (XVIII) and subsequent esterification with ethanol/H2SO4.

1 Alig, L.; Beresini, M.; Weller, T.; et al.; Orally active fibrinogen receptor antagonists. 2. Amidoximes as prodrugs of amidines. J Med Chem 1996, 39, 16, 3139.
2 Weller, T.; Hadvary, P.; Trzeciak, A.; Knopp, D.; Steiner, B.; Edenhofer, A.; Muller, M.; Hurzeler, M.; Alig, L.; Low molecular weight, non-peptide fibrinogen receptor antagonists. J Med Chem 1992, 35, 23, 4393.
3 Castañer, J.; Graul, A.; Merlos, M.; Sibrafiban . Drugs Fut 1998, 23, 12, 1297.
4 Alig, L.; Hadvary, P.; Hurzeler Muller, M.; Muller, M.; Steiner, B.; Weller, T. (F. Hoffmann-La Roche AG); Acetic acid derivs. as medicaments. EP 0656348; JP 1995196592; US 5726185 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 19280 4-cyanobenzoyl chloride 6068-72-0 C8H4ClNO 详情 详情
(VII) 12076 4-Piperidinol; 4-Hydroxypiperidine 5382-16-1 C5H11NO 详情 详情
(VIII) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(IX) 19284 benzyl 4-hydroxy-1-piperidinecarboxylate C13H17NO3 详情 详情
(X) 17430 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate 5292-43-3 C6H11BrO2 详情 详情
(XI) 19286 benzyl 4-[2-(tert-butoxy)-2-oxoethoxy]-1-piperidinecarboxylate C19H27NO5 详情 详情
(XII) 19287 tert-butyl 2-(4-piperidinyloxy)acetate C11H21NO3 详情 详情
(XIII) 61209 CBZ-L-Alanine; (2S)-2-[[(Benzyloxy)carbonyl]amino]propionic acid; N-((Phenylmethoxy)carbonyl)-alanine; Carbobenzyloxy-L-alanine C11H13NO4 详情 详情
(XIV) 19289 tert-butyl 2-[[1-((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)-4-piperidinyl]oxy]acetate C22H32N2O6 详情 详情
(XV) 19290 tert-butyl 2-([1-[(2S)-2-aminopropanoyl]-4-piperidinyl]oxy)acetate C14H26N2O4 详情 详情
(XVI) 19291 tert-butyl 2-[(1-[(2S)-2-[(4-cyanobenzoyl)amino]propanoyl]-4-piperidinyl)oxy]acetate C22H29N3O5 详情 详情
(XVII) 19292 tert-butyl 2-([1-[(2S)-2-([4-[amino(hydroxyimino)methyl]benzoyl]amino)propanoyl]-4-piperidinyl]oxy)acetate C22H32N4O6 详情 详情
(XVIII) 19293 2-([1-[(2S)-2-([4-[amino(hydroxyimino)methyl]benzoyl]amino)propanoyl]-4-piperidinyl]oxy)acetic acid C18H24N4O6 详情 详情
Extended Information