tert-butyl 1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】28933

【品名】tert-butyl 1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinylcarbamate

【CA登记号】

【分子式】C₁₉H₂₆N₄O₅

【分子量】390.4394

【元素组成】C 58.45% H 6.71% N 14.35% O 20.49%

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：(II)

N2-tert-Butyloxycarbonyl-N5-benzyloxycarbonyl-L-arginine (I) is cyclized by treatment with isobutyloxycarbonyl chloride and N-methylmorpholine to the lactam (II). The tert-butyloxycarbonyl group is removed by hydrochloric acid to give the aminolactam (III), which is coupled with N-benzyloxycarbonyl-D-phenylalanyl-L-proline (IV) using, as in the first step, the mixed anhydride method. The resulting tripeptide lactam (V) is reduced with LiAlH4 to an aldehyde, present as the cyclic alpha-aminoalcohol (VI). Deblocking by hydrogenolysis gives RGH-2958. In solution the aldehyde group is either in the cyclic alpha-aminoalcohol form or is hydrated.

参考文献中间体

合成目标

【1】 Rabloczky, Gy.; Bagdy, D.; Bajusz, S.; RGH-2958. Drugs Fut 1985, 10, 10, 829.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	13423	1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate	543-27-1	C₅H₉ClO₂	详情	详情
(B)	28928	4-methylmorpholine	109-02-4	C₅H₁₁NO	详情	详情
(I)	29740	N(5)-[[[(benzyloxy)carbonyl]amino](imino)methyl]-N(2)-(tert-butoxycarbonyl)ornithine	51219-18-2	C₁₉H₂₈N₄O₆	详情	详情
(II)	28933	tert-butyl 1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinylcarbamate		C₁₉H₂₆N₄O₅	详情	详情
(III)	28929	benzyl (E)-amino(3-amino-2-oxo-1-piperidinyl)methylidenecarbamate		C₁₄H₁₈N₄O₃	详情	详情
(IV)	29741	(2S)-1-((2R)-2-[[(benzyloxy)carbonyl]amino]-3-phenylpropanoyl)-2-pyrrolidinecarboxylic acid	7669-64-9	C₂₂H₂₄N₂O₅	详情	详情
(V)	29742	benzyl (E)-amino[3-([[(2S)-1-((2R)-2-[[(benzyloxy)carbonyl]amino]-3-phenylpropanoyl)pyrrolidinyl]carbonyl]amino)-2-oxo-1-piperidinyl]methylidenecarbamate		C₃₆H₄₀N₆O₇	详情	详情
(VI)	29743	benzyl (E)-amino[3-([[(2S)-1-((2R)-2-[[(benzyloxy)carbonyl]amino]-3-phenylpropanoyl)pyrrolidinyl]carbonyl]amino)-2-hydroxy-1-piperidinyl]methylidenecarbamate		C₃₆H₄₂N₆O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

N2-tert-Butoxycarbonyl-N6-benzyloxycarbonyl-L-arginine (I) is converted by treatment with isobutyl oxycarbonyl chloride (A) and N-methylmorpholine (B) to the lactam (II), and the tert-butoxycarbonyl group is cleaved off to give the aminolactam (III), which is coupled with N-tert-butoxycarbonyl-D-phenylalanyl-L-proline (IV) to the tripeptide (V) using the mixed anhydride method as in the first step. The lactam carbonyl is reduced with LiAlH4 to an aldehyde group present as the cyclic a aminoalcohol (VI). Removal of the benzyloxycarbonyl blocking group provides GYKI-14451. In solution the aldehyde group is either in the cyclic alpha-aminoalcohol form or is hydrated.

参考文献中间体

合成目标

【1】 Voutilainen, S.; Valkonen, V.P.; Venho, B.; et al.; Magy Kem Lapja 1982, 27, 2, 358-365.
【2】 Bajusz, S.; Szell, E.; Barabas, E.; Bagdy, D. (Gedeon Richter Ltd.); D-Phenylalanyl-L-prolyl-L-arginine aldehyde sulfate and process for the preparation thereof. DE 3200812; FR 2497799; GB 2091270; JP 57181046; US 4399065; US 4478745 .
【3】 Nogradi, M.; GYKI-14451. Drugs Fut 1985, 10, 1, 23.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	13423	1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate	543-27-1	C₅H₉ClO₂	详情	详情
(B)	28928	4-methylmorpholine	109-02-4	C₅H₁₁NO	详情	详情
(I)	28927	tert-butyl 3-[(amino[[(benzyloxy)carbonyl]imino]methyl)amino]propylcarbamate		C₁₇H₂₆N₄O₄	详情	详情
(II)	28933	tert-butyl 1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinylcarbamate		C₁₉H₂₆N₄O₅	详情	详情
(III)	28929	benzyl (E)-amino(3-amino-2-oxo-1-piperidinyl)methylidenecarbamate		C₁₄H₁₈N₄O₃	详情	详情
(IV)	28932	(2S)-1-[(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl]-2-pyrrolidinecarboxylic acid		C₁₉H₂₆N₂O₅	详情	详情
(V)	28930	tert-butyl (1R)-2-[(2S)-2-([[1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxo-3-piperidinyl]amino]carbonyl)pyrrolidinyl]-1-benzyl-2-oxoethylcarbamate		C₃₃H₄₂N₆O₇	详情	详情
(VI)	28931	tert-butyl (1R)-2-[(2S)-2-([[1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-hydroxy-3-piperidinyl]amino]carbonyl)pyrrolidinyl]-1-benzyl-2-oxoethylcarbamate		C₃₃H₄₄N₆O₇	详情	详情

Extended Information