1,1-dimethylethyl 2-(4-{3-[(4'-cyano[1,1'-biphenyl]-4-yl)oxy]propyl}-1,4-diazepan-1-yl)-2-oxo-1-(1,3-thiazol-4-ylmethyl)ethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】64055

【品名】1,1-dimethylethyl 2-(4-{3-[(4'-cyano[1,1'-biphenyl]-4-yl)oxy]propyl}-1,4-diazepan-1-yl)-2-oxo-1-(1,3-thiazol-4-ylmethyl)ethylcarbamate

【CA登记号】

【分子式】C₃₂H₃₉N₅O₄S

【分子量】589.75896

【元素组成】C 65.17% H 6.67% N 11.87% O 10.85% S 5.44%

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：(VIII)

Alkylation of 4-cyano-4'-hydroxybiphenyl (I) with 1-bromo-3-chloropropane (II) yields the chloropropyl ether (III). This is then condensed with the mono-protected homopiperazine (IV) to furnish (V). Removal of the N-Boc group of (V) to afford amine (VI) is then accomplished by treatment with trifluoroacetic acid in CH2Cl2. Amine (VI) is subsequently coupled with N-Boc-D-thiazolylalanine (VII) in the presence of EDC/DMAP producing amide (VIII). (1,2)

参考文献中间体

合成目标

【1】 Curtis, M.P.; Dwight, W.; Fox, G.B.; Esbenshade, T.A.; Pan, J-B.; Bennani, Y.L.; Hancock, A.A.; Faghih, R.; A-320436: Potent human non-imidazole histamine H3 receptor antagonist. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 240.
【2】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. WO 0166534 .

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)	48735	4-Cyano-4'-hydroxybiphenyl; 4-Hydroxy-4'-cyanodiphenyl; 4'-Cyano-4-biphenylol; 4'-Hydroxy-4-biphenylcarbonitrile	19812-93-2	C₁₃H₉NO	详情	详情
(II)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(III)	57817	4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carbonitrile		C₁₆H₁₄ClNO	详情	详情
(IV)	54079	tert-Butyl 1-homopiperazine carboxylate	n/a	C₁₀H₂₀N₂O₂	详情	详情
(V)	64053	1,1-dimethylethyl 4-{3-[(4'-cyano[1,1'-biphenyl]-4-yl)oxy]propyl}-1,4-diazepane-1-carboxylate		C₂₆H₃₃N₃O₃	详情	详情
(VI)	64054	4'-{[3-(1,4-diazepan-1-yl)propyl]oxy}[1,1'-biphenyl]-4-carbonitrile		C₂₁H₂₅N₃O	详情	详情
(VII)	12882	(2S)-2-[(tert-Butoxycarbonyl)amino]-3-(1,3-thiazol-4-yl)propionic acid		C₁₁H₁₆N₂O₄S	详情	详情
(VIII)	64055	1,1-dimethylethyl 2-(4-{3-[(4'-cyano[1,1'-biphenyl]-4-yl)oxy]propyl}-1,4-diazepan-1-yl)-2-oxo-1-(1,3-thiazol-4-ylmethyl)ethylcarbamate		C₃₂H₃₉N₅O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Acidic cleavage of the N-Boc group of (VIII) furnishes amine (IX). Finally, acylation of (IX) with 2-furoyl chloride (X) leads to the title compound. (1,2)

参考文献中间体

合成目标

【1】 Curtis, M.P.; Dwight, W.; Fox, G.B.; Esbenshade, T.A.; Pan, J-B.; Bennani, Y.L.; Hancock, A.A.; Faghih, R.; A-320436: Potent human non-imidazole histamine H3 receptor antagonist. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 240.
【2】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. WO 0166534 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	64055	1,1-dimethylethyl 2-(4-{3-[(4'-cyano[1,1'-biphenyl]-4-yl)oxy]propyl}-1,4-diazepan-1-yl)-2-oxo-1-(1,3-thiazol-4-ylmethyl)ethylcarbamate		C₃₂H₃₉N₅O₄S	详情	详情
(IX)	64056	4'-[(3-{4-[2-amino-3-(1,3-thiazol-4-yl)propanoyl]-1,4-diazepan-1-yl}propyl)oxy][1,1'-biphenyl]-4-carbonitrile		C₂₇H₃₁N₅O₂S	详情	详情
(X)	26093	2-Furoyl chloride	527-69-5	C₅H₃ClO₂	详情	详情

Extended Information