4-[[(tert-butoxycarbonyl)amino]methyl]cyclohexanecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】23346

【品名】4-[[(tert-butoxycarbonyl)amino]methyl]cyclohexanecarboxylic acid

【CA登记号】

【分子式】C₁₃H₂₃NO₄

【分子量】257.32996

【元素组成】C 60.68% H 9.01% N 5.44% O 24.87%

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)

The intermediate sulfonamide (VII) was prepared by two synthetic routes starting from trans 4-(aminomethyl)cyclohexanecarboxylic acid (I). 1.- The N-Boc derivative (II) was converted to the mixed anhydride with ClCOOMe and then reduced to alcohol (III) using NaBH4. Subsequent conversion of (III) to tosylate, followed by reaction with NaN3, provided azide (IV), which was reduced to amine (V) by hydrogenation over PtO2 (1). Coupling of (V) with 1-naphthalenesulfonyl chloride (VI) produced the corresponding sulfonamide, which by further acid deprotection of the Boc group gave (VII). 2.- In a related procedure, amino acid (I) was coupled with sulfonyl chloride (VI) to afford sulfonamide (VIII). The carboxylic acid of (VIII) was activated as the mixed anhydride with ClCOOEt and then treated with ammonia to provide amide (IX). Reduction of this amide with BH3 in THF then furnished intermediate (VII). 3.- Quinazolindione (X) was treated with phosphoryl chloride in the presence of N,N-dimethylaniline to produce 2,4-dichloroquinazoline (XI). Selective amination of (XI) at position 4 with ammonia yielded (XII), which was finally condensed with amine (VII) to afford the title compound, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Rigollier, P.; Whitebread, S.; Yamaguchi, Y.; Rüeger, H.; Chiesi, M.; Schilling, W.; Criscione, L.; Synthesis and SAR of CGP 71683A, a potent and sele. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.239.
【2】 Yamaguchi, Y.; Rigollier, P.; Rueeger, H.; et al.; Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists. Bioorg Med Chem Lett 2000, 10, 11, 1175.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	23058	4-(aminomethyl)cyclohexanecarboxylic acid	1197-18-8	C₈H₁₅NO₂	详情	详情
(II)	23346	4-[[(tert-butoxycarbonyl)amino]methyl]cyclohexanecarboxylic acid		C₁₃H₂₃NO₄	详情	详情
(III)	23347	tert-butyl [4-(hydroxymethyl)cyclohexyl]methylcarbamate		C₁₃H₂₅NO₃	详情	详情
(IV)	23348	Trans-N-[4-(Aminomethyl)cyclohexylmethyl]carbamic acid tert-butyl ester		C₁₃H₂₆N₂O₂	详情	详情
(V)	23349	tert-butyl [4-(aminomethyl)cyclohexyl]methylcarbamate		C₁₃H₂₆N₂O₂	详情	详情
(VI)	18650	1-naphthalenesulfonyl chloride	85-46-1	C₁₀H₇ClO₂S	详情	详情
(VII)	23351	N-[[4-(aminomethyl)cyclohexyl]methyl]-1-naphthalenesulfonamide		C₁₈H₂₄N₂O₂S	详情	详情
(VIII)	23352	4-[[(1-naphthylsulfonyl)amino]methyl]cyclohexanecarboxylic acid		C₁₈H₂₁NO₄S	详情	详情
(IX)	23353	4-[[(1-naphthylsulfonyl)amino]methyl]cyclohexanecarboxamide		C₁₈H₂₂N₂O₃S	详情	详情
(X)	23354	2,4-Dihydroxyquinazoline;Benzoyleneurea; 2,4(1H,3H)-quinazolinedione; quinazoline-2,4-dione	86-96-4	C₈H₆N₂O₂	详情	详情
(XI)	23355	NSC 75192;2,4-dichloroquinazoline	607-68-1	C₈H₄Cl₂N₂	详情	详情
(XII)	23356	2-chloro-4-quinazolinamine; 2-chloro-4-quinazolinylamine		C₈H₆ClN₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Activation of O-(2-bromobenzyloxycarbonyl)-N-Boc-L-tyrosine (I) as the mixed anhydride (II) with isobutyl chloroformate, followed by coupling with n-octylamine (III), furnished amide (IV). The Boc protecting group of (IV) was then removed by treatment with HCl in dioxan to give amine (V). After activation of trans-4-(aminomethyl)cyclohexanecarboxylic acid (VI) as the mixed anhydride (VII), its coupling with amine (V) provided adduct (VIII). Finally, the cleavage of the Boc protecting group of (VIII) by means of HCl in dioxan yielded the title compound.

参考文献中间体

合成目标

【1】 Hujikata-Okunomiya, A.; Okamoto, S.; Okada, Y.; Matsumoto, Y.; Tada, M.; Tsuda, Y; Wanaka, K.; Development of plasmin selective inhibitors and studies of their structure-activity relationship. Chem Pharm Bull 2000, 48, 2, 184.

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)	43744	(2S)-3-[4-([[(2-bromobenzyl)oxy]carbonyl]oxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid	47689-67-8	C₂₂H₂₄BrNO₇	详情	详情
(II)	43745			C₂₇H₃₂BrNO₉	详情	详情
(III)	27374	1-octanamine	111-86-4	C₈H₁₉N	详情	详情
(IV)	43746	2-bromobenzyl 4-[(2S)-2-[(tert-butoxycarbonyl)amino]-3-(octylamino)-3-oxopropyl]phenyl carbonate		C₃₀H₄₁BrN₂O₆	详情	详情
(V)	43747	4-[(2S)-2-amino-3-(octylamino)-3-oxopropyl]phenyl 2-bromobenzyl carbonate		C₂₅H₃₃BrN₂O₄	详情	详情
(VI)	23346	4-[[(tert-butoxycarbonyl)amino]methyl]cyclohexanecarboxylic acid		C₁₃H₂₃NO₄	详情	详情
(VII)	43748			C₁₈H₃₁NO₆	详情	详情
(VIII)	43749	2-bromobenzyl 4-[(2S)-2-[[(4-[[(tert-butoxycarbonyl)amino]methyl]cyclohexyl)carbonyl]amino]-3-(octylamino)-3-oxopropyl]phenyl carbonate		C₃₈H₅₄BrN₃O₇	详情	详情

Extended Information