1-isocyanatocyclohexane; cyclohexyl isocyanate -Drug Synthesis Database

【结构式】

【分子编号】18108

【品名】1-isocyanatocyclohexane; cyclohexyl isocyanate

【CA登记号】3173-53-3

【分子式】C₇H₁₁NO

【分子量】125.17048

【元素组成】C 67.17% H 8.86% N 11.19% O 12.78%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(C)

FG5803 is obtained in a three-step synthesis: In the first step 4-(4-fluorophenyl)-4,4-ethylenedioxybutylchloride (A) reacts with piperazine (B) to give 1-[4-(4-fluorophenyl)-4,4-ethylenedioxybutyl]piperazine (I), which is reacted with cyclohexylisocyanate (C) to form 4-[4-(4-fluorophenyl)-4,4-ethylenedioxybutyl]-N-cyclohexyl-1-piperazinecarboxamide (II). The protecting group is removed by HCl in ethanol and the final product is isolated, 4-[4-(4-fluorophenyl)-4-oxobutyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (III).

参考文献中间体

合成目标

【1】 Bjork, A.; Fex, T.; Olsson, K.; Abramo, A.; Gustafsson, B.; Christensson, E. (Ferrosan AB); Novel 1-piperazinecarboxamide derivs.. EP 0136274; ES 8704917; ES 8705411; ES 8802039; JP 1985501956; US 4935419; WO 8500811 .
【2】 Lundstedt, T.; Bjork, A.; Pettersson, G.; Svartengren, J.; Christensson, E.; Gustavsson, B.; FG5803. Drugs Fut 1990, 15, 12, 1176.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(A)	28203	2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane	3308-94-9	C₁₂H₁₄ClFO₂	详情	详情
(I)	31226	1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]piperazine		C₁₆H₂₃FN₂O₂	详情	详情
(II)	31227	N-cyclohexyl-4-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-1-piperazinecarboxamide		C₂₃H₃₄FN₃O₃	详情	详情
(C)	18108	1-isocyanatocyclohexane; cyclohexyl isocyanate	3173-53-3	C₇H₁₁NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of aminothiophene (I) with cyclohexyl isocyanate (II) in refluxing toluene afforded urea (III). Then, treatment with ethanolic KOH gave the pyrimidine dione system.

参考文献中间体

合成目标

【1】 Romeo, G.; et al.; Synthesis of new thieno[2,3-d]pyrimidine-2,4(1H, 3H)-diones with analgesic and anti-inflammatory activities. Arzneim-Forsch Drug Res 1998, 48, 2, 167-172.

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)	18107	ethyl 2-amino-4,5-dimethyl-3-thiophenecarboxylate	4815-24-1	C₉H₁₃NO₂S	详情	详情
(II)	18108	1-isocyanatocyclohexane; cyclohexyl isocyanate	3173-53-3	C₇H₁₁NO	详情	详情
(III)	18109	ethyl 2-[[(cyclohexylamino)carbonyl]amino]-4,5-dimethyl-3-thiophenecarboxylate		C₁₆H₂₄N₂O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The trans-3-amino-2-piperidineacetic acid derivative (I), obtained as a 5:1 mixture of (2S,3R)- and (2R,3S)-isomers, was condensed with cyclohexyl isocyanate (II) to produce urea (III). Base-catalyzed cyclization of (III) gave rise to the dioxo pyridopyrimidine (IV). Acid cleavage of the Boc group of (IV) afforded the corresponding mixture of enantiomeric trans-amines (V). Acylation of amines (V) with N-Boc-L-tryptophan (VI) by means of BOP as the coupling reagent furnished the corresponding mixture of diastereomeric amides from which the target isomer was isolated by preparative TLC.

参考文献中间体

合成目标

【1】 Bartolomé-Nebreda, J.M.; et al.; 5-(Tryptophyl) amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based potent and selective CCK1 receptor antagonists: Structure-activity relationship studies on the substituent at N2-position. J Med Chem 2001, 44, 13, 2219.

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)	44208	ethyl 2-[(2S,3R)-3-[(tert-butoxycarbonyl)amino]piperidinyl]acetate		C₁₄H₂₆N₂O₄	详情	详情
(II)	18108	1-isocyanatocyclohexane; cyclohexyl isocyanate	3173-53-3	C₇H₁₁NO	详情	详情
(III)	51348	ethyl 2-[(2S,3R)-3-[(tert-butoxycarbonyl)amino]-1-[(cyclohexylamino)carbonyl]piperidinyl]acetate		C₂₁H₃₇N₃O₅	详情	详情
(IV)	51349	tert-butyl (4aS,5R)-2-cyclohexyl-1,3-dioxooctahydro-1H-pyrido[1,2-c]pyrimidin-5-ylcarbamate		C₁₉H₃₁N₃O₄	详情	详情
(V)	51350	(4aS,5R)-5-amino-2-cyclohexylhexahydro-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione		C₁₄H₂₃N₃O₂	详情	详情
(VI)	16114	N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid	13139-14-5	C₁₆H₂₀N₂O₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VI)

Hydrolysis of 3-bromobenzonitrile (I) by means of sodium perborate leads to amide (II). Subsequent Suzuki coupling of 3-bromobenzamide (II) with 3-methoxyphenylboronic acid (III) furnishes the biphenyl compound (IV). The methyl ether group of (IV) is then cleaved employing BBr3 to yield phenol (V). This is finally coupled with cyclohexyl isocyanate (VI) to produce the title carbamate.

参考文献中间体

合成目标

【1】 Kathuria, S.; Gaetani, S.; Fegley, D.; Valiño, M.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; La Rana, G.; Calignano, A.; Giustino, A.; Tattoli, M.; Palmery, M.; Cuomo, V.; Piomelli, D.; Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 2003, 9, 1, 76.

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)	26573	3-bromobenzonitrile	6952-59-6	C₇H₄BrN	详情	详情
(II)	63206	3-bromobenzamide		C₇H₆BrNO	详情	详情
(III)	29426	3-methoxyphenylboronic acid	10365-98-7	C₇H₉BO₃	详情	详情
(IV)	63207	3'-methoxy[1,1'-biphenyl]-3-carboxamide		C₁₄H₁₃NO₂	详情	详情
(V)	63208	3'-hydroxy[1,1'-biphenyl]-3-carboxamide		C₁₃H₁₁NO₂	详情	详情
(VI)	18108	1-isocyanatocyclohexane; cyclohexyl isocyanate	3173-53-3	C₇H₁₁NO	详情	详情

Extended Information