2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]ethyl methanesulfonate -Drug Synthesis Database

【结构式】

【分子编号】38442

【品名】2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]ethyl methanesulfonate

【CA登记号】

【分子式】C₂₃H₂₇Cl₂NO₈S

【分子量】548.44072

【元素组成】C 50.37% H 4.96% Cl 12.93% N 2.55% O 23.34% S 5.85%

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：(XXVI)

Asymmetric dihydroxylation of intermeddiate silylated olefin (XII) employing potassium ferricyanide in the presence of osmium tetraoxide and the chiral auxiliary hydroquinidine 1,4-phthalazindiyl diether produced diol (XVIII). After conversion of the primary hydroxyl group of (XVIII) to the corresponding tosylate (XIX), displacement with ethanolamine yielded hydroxy amine (XX). Protection of (XX) as the Boc derivative (XXI), followed by cyclization under Mitsunobu conditions gave rise to morpholine (XXII). The Boc and silyl groups of (XXII) were then deprotected with HCl in dioxan, and the deprotected morpholine (XXIII) was acylated with 3,4,5-trimethoxybenzoyl chloride (XXIV) to produce amide (XXV). The alcohol group of (XXV) was then converted to mesylate (XXVI) using methanesulfonyl chloride and triethylamine. Optionally, the alchohol group was subjected to Swern oxidation, affording aldehyde (XXVII).

参考文献中间体

合成目标

【1】 Kurata, H.; Ito, K.; Nakajima, K.; Yamaguchi, T.; Ishibashi, K.; Fukuzawa, T.; Nishi, T. (Sankyo Co., Ltd.); Azaheterocyclic cpds. having tachykinin receptor antagonist activity; NK1 and NK2. EP 0776893; JP 1998152478; JP 1998182649; JP 1998182650 .
【2】 Nishi, T.; Yamaguchi, T. (Sankyo Co., Ltd.); Salts of optically active sulfoxide deriv.. EP 0987269; JP 1999043490; WO 9854191 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(XII)	38430	tert-butyl[[3-(3,4-dichlorophenyl)-3-butenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl 3-(3,4-dichlorophenyl)-3-butenyl ether		C₁₆H₂₄Cl₂OSi	详情	详情
(XVIII)	38435	(2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-1,2-butanediol		C₁₆H₂₆Cl₂O₃Si	详情	详情
(XIX)	38436	(2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-2-hydroxybutyl 4-methylbenzenesulfonate		C₂₃H₃₂Cl₂O₅SSi	详情	详情
(XX)	38437	(2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-1-[(2-hydroxyethyl)amino]-2-butanol		C₁₈H₃₁Cl₂NO₃Si	详情	详情
(XXI)	38438	tert-butyl (2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-2-hydroxybutyl(2-hydroxyethyl)carbamate		C₂₃H₃₉Cl₂NO₅Si	详情	详情
(XXII)	38439	tert-butyl (2R)-2-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-(3,4-dichlorophenyl)-4-morpholinecarboxylate		C₂₃H₃₇Cl₂NO₄Si	详情	详情
(XXIII)	38440	2-[(2R)-2-(3,4-dichlorophenyl)morpholinyl]-1-ethanol		C₁₂H₁₅Cl₂NO₂	详情	详情
(XXIV)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(XXV)	38441	[(2R)-2-(3,4-dichlorophenyl)-2-(2-hydroxyethyl)morpholinyl](3,4,5-trimethoxyphenyl)methanone		C₂₂H₂₅Cl₂NO₆	详情	详情
(XXVI)	38442	2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]ethyl methanesulfonate		C₂₃H₂₇Cl₂NO₈S	详情	详情
(XXVII)	38443	2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]acetaldehyde		C₂₂H₂₃Cl₂NO₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

The title compound was then prepared by two alternative procedures: Piperidine (VII) was alkylated with mesylate (XXVI) to produce the desired tertiary amine. Alternatively, aldehyde (XXVII) was reductively condensed with piperidine (VII) in the presence of NaBH3CN. The compound was finally converted to the hydrochloride salt.

参考文献中间体

合成目标

【1】 Kurata, H.; Ito, K.; Nakajima, K.; Yamaguchi, T.; Ishibashi, K.; Fukuzawa, T.; Nishi, T. (Sankyo Co., Ltd.); Azaheterocyclic cpds. having tachykinin receptor antagonist activity; NK1 and NK2. EP 0776893; JP 1998152478; JP 1998182649; JP 1998182650 .
【2】 Nishi, T.; Yamaguchi, T. (Sankyo Co., Ltd.); Salts of optically active sulfoxide deriv.. EP 0987269; JP 1999043490; WO 9854191 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	38426	(2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine] 2-oxide	191673-15-1	C₁₂H₁₅NOS	详情	详情
(XXVI)	38442	2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]ethyl methanesulfonate		C₂₃H₂₇Cl₂NO₈S	详情	详情
(XXVII)	38443	2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]acetaldehyde		C₂₂H₂₃Cl₂NO₆	详情	详情

Extended Information