4-Quinuclidinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】11766

【品名】4-Quinuclidinecarboxamide

【CA登记号】

【分子式】C₈H₁₄N₂O

【分子量】154.21204

【元素组成】C 62.31% H 9.15% N 18.17% O 10.37%

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：(VII)

A new synthesis of [14C]-labeled E-1040 with the label in the quinuclidine ring has been reported: The reduction of [14C]-labeled bromoacetic acid (I) with borane-dimethyl sulfide complex in ethyl ether gives 2-bromoethanol (II), which is condensed with piperidine-4-carboxamide (III) by means of K2CO3 and KI in refluxing isopropanol, yielding the [14C]-labeled 1-(2-hydroxyethyl)piperidine-4-carboxamide (IV). The reaction of (IV) with SOCl2 in refluxing acetonitrile affords the 1-(2-chloroethyl)piperidine-4-carbonitrile (V), which is cyclized by means of lithium diisopropylamide in THF, giving the quinuclidine (VI). The hydrolysis of (VI) with sulfuric acid gives [14C]-labeled quinuclidine-4-carboxamide (VII), which is finally condensed with the 3-chloromethylcephalosporin (VIII) by means of Na in acetone and a treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Woolley, G.T.; Sugiyama, I.; Yamauchi, H.; Mizuo, H.; Synthesis of 14C-labelled cefclidin (E1040). J Label Compd Radiopharm 1992, 31, 9, 663.

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)	23660	2-Bromoacetic acid	79-08-3	C₂H₃BrO₂	详情	详情
(I)	45074	2-bromoacetic acid		C₂H₃BrO₂	详情	详情
(II)	10059	Ethylene bromohydrin; 2-Bromo-1-ethanol	540-51-2	C₂H₅BrO	详情	详情
(II)	45075	2-bromo-1-ethanol		C₂H₅BrO	详情	详情
(III)	11762	4-Piperidinecarboxamide; Isonipecotamide	39546-32-2	C₆H₁₂N₂O	详情	详情
(IV)	11763	1-(2-Hydroxyethyl)-4-piperidinecarboxamide		C₈H₁₆N₂O₂	详情	详情
(IV)	45076	1-(2-hydroxyethyl)-4-piperidinecarboxamide		C₈H₁₆N₂O₂	详情	详情
(V)	11764	1-(2-Chloroethyl)-4-piperidinecarbonitrile		C₈H₁₃ClN₂	详情	详情
(V)	45077	1-(2-chloroethyl)-4-piperidinecarbonitrile		C₈H₁₃ClN₂	详情	详情
(VI)	11765	4-Quinuclidinecarbonitrile		C₈H₁₂N₂	详情	详情
(VI)	45078	4-quinuclidinecarbonitrile		C₈H₁₂N₂	详情	详情
(VII)	11766	4-Quinuclidinecarboxamide		C₈H₁₄N₂O	详情	详情
(VII)	45079	4-quinuclidinecarboxamide		C₈H₁₄N₂O	详情	详情
(VIII)	11767	4-methoxybenzyl (6R,7R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetyl]amino]-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₂₁H₂₁ClN₆O₆S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The reaction of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(methoxyimino)acetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid (I) with N-methyl-N-(trimethylsilyl)trifluoroacetamide and then with iodotrimethylsilane in dichloromethane gives the corresponding silylated 3-iodomethyl derivative (II), which is then treated with 4-carbamoylquinuclidine (III) in acetonitrile.

参考文献中间体

合成目标

【1】 Kamiya, T.; Machida, Y.; Negi, S.; Nomoto, S.; Saito, I.; Sugiyama, I.; Yamauchi, H. (Eisai Co., Ltd.); Cephem cpds. having at the 3-position a (1,4-methylene-1-piperidinio)methyl group or a (1-quinuclidinio)methyl group. AU 8652240; EP 0188255; ES 8703885; JP 1987030786; JP 1987123189; US 4748171; US 5010188 .
【2】 Prous, J.; Castaner, J.; E-1040. Drugs Fut 1988, 13, 2, 117.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	21859	2,2,2-trifluoro-N-methyl-N-(trimethylsilyl)acetamide	C₆H₁₂F₃NOSi	详情	详情
(I)	21858	(7R)-3-[(acetoxy)methyl]-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	C₁₅H₁₆N₆O₇S₂	详情	详情
(II)	21860	trimethylsilyl (7R)-3-(iodomethyl)-7-[(2-(methoxyimino)-2-[5-[(trimethylsilyl)amino]-1,2,4-thiadiazol-3-yl]acetyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	C₁₉H₂₉IN₆O₅S₂Si₂	详情	详情
(III)	11766	4-Quinuclidinecarboxamide	C₈H₁₄N₂O	详情	详情

Extended Information