(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】25929

【品名】(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propionic acid

【CA登记号】

【分子式】C₁₄H₁₈FNO₄

【分子量】283.2996632

【元素组成】C 59.36% H 6.4% F 6.71% N 4.94% O 22.59%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The reaction of N-(tert-butoxycarbonyl)-L-4-fluorophenylalanine (I) with 4-hydroxypiperidine (II) by means of triethylamine, EDC and HOBT in dichloromethane gives the expected piperidide (III), which is deprotected with with HCl in dioxane to afford (IV) with a free amino group that is condensed with 5-chloro-1H-indole-2-carboxylic acid (V) by means of triethylamine, EDC and HOBT as before.

参考文献中间体

合成目标

【1】 Hoover, D.J.; et al.; Indole-2-carboxamide inhibitors of human liver glycogen phosphorylase. J Med Chem 1998, 41, 16, 2934.
【2】 Hulin, B.; Hoover, D.J.; Treadway, J.L.; Martin, W.H.; Phillips, D. (Pfizer Inc.); Substd. N-(indole-2-carbonyl)-glycinamides and derivs. as glycogen phosphorylase inhibitors. EP 0832065; WO 9639384 .

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)	25929	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propionic acid		C₁₄H₁₈FNO₄	详情	详情
(II)	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(III)	25930	tert-butyl (1S)-1-(4-fluorobenzyl)-2-(4-hydroxy-1-piperidinyl)-2-oxoethylcarbamate		C₁₉H₂₇FN₂O₄	详情	详情
(IV)	25931	(2S)-2-amino-3-(4-fluorophenyl)-1-(4-hydroxy-1-piperidinyl)-1-propanone		C₁₄H₁₉FN₂O₂	详情	详情
(V)	25932	5-Chloroindole-2-carboxylic acid; 5-Chloro-1H-indole-2-carboxylic acid	10517-21-2	C₉H₆ClNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

The coupling and deprotection cycles was continued with N-Boc-L-(3-pyridyl)alanine (XII), N-Boc-S-(4-methylbenzyloxy-carbonyl)-D-cysteine (IV), and N-Boc-L-4-fluorophenylalanine (XV), yielding the peptide resins (XIII), (XIV) and (XVI), respectively.

参考文献中间体

合成目标

【1】 Taylor, J.E.; Hocart, S.J.; Murphy, W.A.; Coy, D.H.; Jian, R.; Highly potent cyclic disulfide antagonists of somatostatin. J Med Chem 1999, 42, 11, 1863.
【2】 Rossowski, W.J.; Cheng, B.-L.; Jiang, N.-Y.; Coy, D.-H.; Examination of somatostatin involvement in the inhibitory action of GIP, GLP-1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue. Br J Pharmacol 1998, 125, 1081.
【3】 Murphy, W.; Coy, D.H.; Morgan, B. (Biomeasure Inc.; Tulane Educational Fund); Somatostatin antagonists. WO 9824807 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	31371	(2R)-2-[(tert-butoxycarbonyl)amino]-3-([[(4-methylbenzyl)oxy]carbonyl]sulfanyl)propionic acid	C₁₇H₂₃NO₆S	详情	详情
(XI)	31377	S-[(2R,5S,8S)-8-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-1-yl] O-(4-methylbenzyl) carbonothioate	C₅₆H₆₅ClN₈O₉S	详情	详情
(XII)	34944	(2S)-2-[(tert-butoxycarbonyl)(3-pyridinyl)amino]propionic acid	C₁₃H₁₈N₂O₄	详情	详情
(XIII)	31376	S-[(2R,5S,8S)-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-8-[[(2R)-2-[[(2S)-2-amino-3-(3-pyridinyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(tert-butyl)-16-(2-chlorophenyl)-4,7,14-trioxo-15-oxa-3,6,13-triazahexadec-	C₆₄H₇₃ClN₁₀O₁₀S	详情	详情
(XIV)	31379	S-[(2R,5S,8S,11R,14S,17S)-17-amino-2-([[(1S)-2-amino-1-(2-naphthylmethyl)-2-oxoethyl]amino]carbonyl)-5-(tert-butyl)-8-[4-([[(2-chlorobenzyl)oxy]carbonyl]amino)butyl]-11-(1H-indol-3-ylmethyl)-22-(4-methylphenyl)-4,7,10,13,16,20-hexaoxo-14-(3-pyridiny	C₇₆H₈₆ClN₁₁O₁₃S₂	详情	详情
(XV)	25929	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propionic acid	C₁₄H₁₈FNO₄	详情	详情
(XVI)	34945		C₉₀H₁₀₂ClFN₁₂O₁₆S₂	详情	详情

Extended Information