(2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine] 2-oxide -Drug Synthesis Database

【结构式】

【分子编号】38426

【品名】(2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine] 2-oxide

【CA登记号】191673-15-1

【分子式】C₁₂H₁₅NOS

【分子量】221.32324

【元素组成】C 65.12% H 6.83% N 6.33% O 7.23% S 14.49%

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)

Lithiation of 2-bromobenzyl thiol (I) followed by addition to N-Boc-4-piperidone (II) gave mercapto alcohol (III), which was cyclized to the spiro derivative by refluxing in 4N sulfuric acid. Protection as the tert-butyl carbamate (IV), followed by oxidation with m-chloroperbenzoic acid produced sulfoxide (V). After acid cleavage of the Boc protecting group of (V), resolution with (S)-(+)-mandelic acid furnished the required (S)-enantiomer (VII). Alternatively, asymmetric oxidation of sulfide (IV) with (3'S,2R)-(-)-N-(phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine produced the (S)-sulfoxide (VI), which was further deprotected to (VII) with HCl in dioxan.

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
(I)	38421	(2-bromophenyl)methanethiol; 2-bromobenzylhydrosulfide		C₇H₇BrS	详情	详情
(II)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(III)	38422	tert-butyl 4-hydroxy-4-[2-(sulfanylmethyl)phenyl]-1-piperidinecarboxylate		C₁₇H₂₅NO₃S	详情	详情
(IV)	38423	Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester	173944-03-1	C₁₇H₂₃NO₂S	详情	详情
(V)	38424	(2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester, 2-oxide	191673-21-9	C₁₇H₂₃NO₃S	详情	详情
(VI)	38425	Spiro[benzo[C]thiophene-1(3H),4'-piperidine]-1'-carboxylic acid, 1,1-dimethylethyl ester, 2-oxide	173944-04-2	C₁₇H₂₃NO₃S	详情	详情
(VII)	38426	(2S)-Spiro[benzo[C]thiophene-1(3H),4'-piperidine] 2-oxide	191673-15-1	C₁₂H₁₅NOS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

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