2-chloro-4-(1-pyrrolidinyl)benzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】27547

【品名】2-chloro-4-(1-pyrrolidinyl)benzoyl chloride

【CA登记号】

【分子式】C₁₁H₁₁Cl₂NO

【分子量】244.11988

【元素组成】C 54.12% H 4.54% Cl 29.05% N 5.74% O 6.55%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

Horner-Emmons condensation of benzazepinone (I) with triethyl phosphonoacetate gave unsaturated ester (II). Subsequent reductive treatment of (II) with Mg in MeOH produced the saturated ester (III) with concomitant cleavage of the tosyl group. 2-Chloro-4-(1-pyrrolidinyl)benzoyl chloride (V) (prepared by reaction of the corresponding carboxylic acid (IV) with SOCl2) was then condensed with benzazepine (III) to produce benzamide (VI). Hydrolysis of the methyl ester function of (VI) yielded the racemic carboxylic acid (VII), which was resolved by means of esterification with (R)-2-heptanol, followed by chromatographic separation of the diastereomeric mixture. After saponification of the required diastereoisomeric ester (VIII), the resulting (R)-carboxylic acid was finally coupled with isopropylamine using diethylcyanophosphate as the condensing reagent.

参考文献中间体

合成目标

【1】 Kondo, K.; et al.; Characterization of orally active nonpeptide vasopressin V2 receptor agonist. Synthesis and biological evaluation of both the (5R)- and (5S)-enantioisomers of 2-[1-(2-chloro-4-pyrrolidin-1yl-benzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]-N-isopropylace. J Med Chem 2002, 45, 17, 3805.
【2】 Ogawa, H.; Kondo, K.; Shinohara, T.; Kan, K.; Tanada, Y.; Kurimura, M.; Morita, S.; Uchida, M.; Mori, T.; Tominaga, M.; Yabuuchi, Y. (Otsuka Pharmaceutical Co., Ltd.); Benzazepine derivs. with vasopressin agonistic activity. EP 0877736; JP 1998081668; US 6096736; WO 9722591 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
	42235	Diethyl phosphorocyanidate; Diethyl cyanophosphonate; Cyanophosphonic acid diethyl ester; Diethyl phosphoryl cyanide; DEPC	2942-58-7	C₅H₁₀NO₃P	详情	详情
(I)	14763	1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₇NO₃S	详情	详情
(II)	27544	ethyl 2-[1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene]acetate		C₂₁H₂₃NO₄S	详情	详情
(III)	27545	methyl 2-(2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl)acetate		C₁₃H₁₇NO₂	详情	详情
(IV)	27546	2-chloro-4-(1-pyrrolidinyl)benzoic acid		C₁₁H₁₂ClNO₂	详情	详情
(V)	27547	2-chloro-4-(1-pyrrolidinyl)benzoyl chloride		C₁₁H₁₁Cl₂NO	详情	详情
(VI)	27548	methyl 2-[1-[2-chloro-4-(1-pyrrolidinyl)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]acetate		C₂₄H₂₇ClN₂O₃	详情	详情
(VII)	27549	2-[1-[2-chloro-4-(1-pyrrolidinyl)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]acetic acid		C₂₃H₂₅ClN₂O₃	详情	详情
(VIII)	27550	(1R)-1-methylhexyl 2-[(5R)-1-[2-chloro-4-(1-pyrrolidinyl)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]acetate		C₃₀H₃₉ClN₂O₃	详情	详情

Extended Information