tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate -Drug Synthesis Database

【结构式】

【分子编号】26836

【品名】tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate

【CA登记号】

【分子式】C₁₄H₂₈N₄O₄

【分子量】316.40088

【元素组成】C 53.15% H 8.92% N 17.71% O 20.23%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

Coupling of thiazolopyridine (I) with amine (II) in the presence of EDC and HOBt provided amide (III). Deprotection of the Fmoc group of (III) was effected with piperidine in CH2Cl2 and the resulting amine (IV) was condensed with benzylsulfonyl chloride (V) to afford sulfonamide (VI). Finally, both Boc protecting groups of (VI) were removed with TFA to yield the title guanidine as the bis(trifluoroacetate) salt.

参考文献中间体

合成目标

【1】 Wagner, J.; Kallen, J.; Ehrhardt, C.; Evenou, J.-P.; Wagner, D.; Rational design, synthesis, and X-ray structure of selective noncovalent thrombin inhibitors. J Med Chem 1998, 41, 19, 3664.

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)	26832	(3R,6S,8aS)-6-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxohexahydro-5H-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid		C₂₃H₂₂N₂O₅S	详情	详情
(II)	26836	tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₁₄H₂₈N₄O₄	详情	详情
(III)	26833	9H-fluoren-9-ylmethyl (3R,6S,8aS)-3-[(Z)-7-[(tert-butoxycarbonyl)amino]-11,11-dimethyl-9-oxo-10-oxa-2,6,8-triaza-7-dodecen-1-anoyl]-5-oxohexahydro-5H-[1,3]thiazolo[3,2-a]pyridin-6-ylcarbamate		C₃₇H₄₈N₆O₈S	详情	详情
(IV)	26834	tert-butyl (Z)-[[3-([[(3R,6S,8aS)-6-amino-5-oxohexahydro-5H-[1,3]thiazolo[3,2-a]pyridin-3-yl]carbonyl]amino)propyl]amino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₂₂H₃₈N₆O₆S	详情	详情
(V)	25151	phenylmethanesulfonyl chloride	1939-99-7	C₇H₇ClO₂S	详情	详情
(VI)	26835	tert-butyl (Z)-([3-[([(3R,6S,8aS)-6-[(benzylsulfonyl)amino]-5-oxohexahydro-5H-[1,3]thiazolo[3,2-a]pyridin-3-yl]carbonyl)amino]propyl]amino)[(tert-butoxycarbonyl)amino]methylidenecarbamate		C₂₉H₄₄N₆O₈S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

1,3-Diaminopropane (I) is mono-protected with benzyl chloroformate, producing carbamate (II). Coupling of (II) with N,N'-bis-Boc-S-methylisothiourea (III) yields the Boc-protected guanidine (IV). The benzyloxycarbonyl group of (IV) is then removed by catalytic hydrogenolysis to furnish the noragmatine derivative (V)

参考文献中间体

合成目标

【1】 Szelke, M.; Evans, D.M.; Jones, D.M. (Ferring AB); Kininogen inhibitors. WO 9507291 .

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)	19331	3-aminopropylamine; 1,3-propanediamine	109-76-2	C₃H₁₀N₂	详情	详情
(II)	62059	benzyl 3-aminopropylcarbamate		C₁₁H₁₆N₂O₂	详情	详情
(III)	22345	tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₁₂H₂₂N₂O₄S	详情	详情
(IV)	62060	benzyl 3-({[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl}amino)propylcarbamate		C₂₂H₃₄N₄O₆	详情	详情
(V)	26836	tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₁₄H₂₈N₄O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Coupling between N-Boc-D-(4-chlorophenyl)alanine succinimidyl ester (VI) and L-naphthylalanine methyl ester (VII) affords the protected dipeptide (VIII). The methyl ester group of (VIII) is hydrolyzed by means of LiOH to produce the carboxylic acid (IX), which is subsequently coupled to the di-Boc-protected noragmatine (V), yielding amide (X). Finally, acidic cleavage of the Boc protecting groups of (X) leads to the title compound

参考文献中间体

合成目标

【1】 Szelke, M.; Evans, D.M.; Jones, D.M. (Ferring AB); Kininogen inhibitors. WO 9507291 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	26836	tert-butyl (Z)-[(3-aminopropyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate	C₁₄H₂₈N₄O₄	详情	详情
(VI)	62061	tert-butyl (1R)-1-(4-chlorobenzyl)-2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethylcarbamate	C₁₈H₂₁ClN₂O₆	详情	详情
(VII)	62062	methyl (2S)-2-amino-3-(1-naphthyl)propanoate	C₁₄H₁₅NO₂	详情	详情
(VIII)	62063	methyl (2S)-2-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propanoyl]amino}-3-(1-naphthyl)propanoate	C₂₈H₃₁ClN₂O₅	详情	详情
(IX)	62064	(2S)-2-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-chlorophenyl)propanoyl]amino}-3-(1-naphthyl)propanoic acid	C₂₇H₂₉ClN₂O₅	详情	详情
(X)	62065	tert-butyl (1R,4S,11Z)-11-[(tert-butoxycarbonyl)amino]-1-(4-chlorobenzyl)-15,15-dimethyl-4-(1-naphthylmethyl)-2,5,13-trioxo-14-oxa-3,6,10,12-tetraaza-11-hexadecen-1-ylcarbamate	C₄₁H₅₅ClN₆O₈	详情	详情

Extended Information