3-quinuclidinecarbonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】20291

【品名】3-quinuclidinecarbonyl chloride

【CA登记号】

【分子式】C₈H₁₂ClNO

【分子量】173.64212

【元素组成】C 55.34% H 6.97% Cl 20.42% N 8.07% O 9.21%

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 synthesis of EO 122 starts from quinuclidine-3-carboxylic acid (I), which is converted to the acid chloride (II) by oxalyl chloride. The addition of 2,6-dimethylaniline (III) to the acid chloride yields EO-122.

参考文献中间体

合成目标

【1】 Kaplinsky, E.; Bruckstein, R.; Kariv, E.; Oppenheimer, E.; Cohen, S.; A preclinical study of EO-122, a new lidocaine-lik. Angiology 1980, 31, 410.
【2】 Renk, E.; Grob, C.A.; Studie in the quinudidine line. 3-Quinudialine-car. Helv Chim Acta 1954, 37, 1689.
【3】 Oppenheimer, E.; Binah, O.; EO-122. Drugs Fut 1988, 13, 8, 724.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(I)	20290	3-quinuclidinecarboxylic acid		C₈H₁₃NO₂	详情	详情
(II)	20291	3-quinuclidinecarbonyl chloride		C₈H₁₂ClNO	详情	详情
(III)	17527	2,6-Xylidine; 2,6-Dimethylaniline; 2,6-Dimethylphenylamine	87-62-7	C₈H₁₁N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

A new synthesis of sabcomeline hydrochloride has been described: The hydrolysis of quinuclidine-3-carboxylic acid ethyl ester (I) with refluxing aqueous HCl gives the corresponding acid (II), which by reaction with thionyl chloride in refluxing dichloromethane yields the expected acyl chloride (III). The reaction of (III) with O-methylhydroxylamine in chloroform/pyridine affords N-methoxyquinuclidine-3-carboxamide (IV), which by reaction with triphenylphosphine/CCl4 in refluxing acetonirile is converted into the imidoyl chloride (V). The reaction of (V) with NaCN in hot DMSO gives 2-(methoxyimino)-2-(3-quinuclidinyl)acetonitrile (VI) as a mixture of the (E)- and (Z)-isomers that is resolved by column chromatography yielding the (Z)-isomer (VII). Finally, this compound (VII) is submitted to optical resolution with (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate [(R)-(-)-BNHP].

参考文献中间体

合成目标

【1】 Bromidge, S.M.; Brown, F.; Cassidy, F.; et al.; Design of [R-(Z)]-(+)-alpha-(methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitrile (SB 202026), a functionally selective azabicyclic muscarinic M1 agonist incorporating the N-methoxy imidoyl nitrile group as a novel ester bioisostere. J Med Chem 1997, 40, 26, 4265.

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)	20289	ethyl 3-quinuclidinecarboxylate; 3-carbethoxyquinuclidine; 1-azabicyclo[2.2.2]octane-3-ethylcarboxylate	6238-33-1	C₁₀H₁₇NO₂	详情	详情
(II)	20290	3-quinuclidinecarboxylic acid		C₈H₁₃NO₂	详情	详情
(III)	20291	3-quinuclidinecarbonyl chloride		C₈H₁₂ClNO	详情	详情
(IV)	16921	N-methoxy-3-quinuclidinecarboxamide		C₉H₁₆N₂O₂	详情	详情
(V)	16922	N-methoxy-3-quinuclidinecarboximidoyl chloride		C₉H₁₅ClN₂O	详情	详情
(VII)	16923	N-methoxy-3-quinuclidinecarboximidoyl cyanide		C₁₀H₁₅N₃O	详情	详情

Extended Information