2-(4-methoxyphenyl)-4-oxo-4,5-dihydro-1,5-benzothiazepin-3-yl acetate -Drug Synthesis Database

【结构式】

【分子编号】62452

【品名】2-(4-methoxyphenyl)-4-oxo-4,5-dihydro-1,5-benzothiazepin-3-yl acetate

【CA登记号】

【分子式】C₁₈H₁₅NO₄S

【分子量】341.38744

【元素组成】C 63.33% H 4.43% N 4.1% O 18.75% S 9.39%

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：(XXXIV)

The racemic thiazepinone (XXXIII) has been converted to the pure enantiomer (VIII) through a different strategy. Oxidation of hydroxy lactam (XXXIII) by means of DMSO and Ac2O produced the enol ester (XXXV). Basic hydrolysis of (XXXI) gave rise to the keto lactam (XXXV). This was then subjected to asymmetric reduction utilizing a reducing reagent generated in situ from NaBH4 and (S)-tert-leucine to afford the intermediate thiazepinone (VIII)

参考文献中间体

合成目标

【1】 Yamada, S.; Mori, Y.; Morimatsu, K.; Ishizu, Y.; Ozaki, Y.; Yoshioka, R.; Nakatani, T.; Seko, H.; Asymmetric reduction of a 1,5-benzothiazepine derivative with sodium borohydride-(S)-alpha-amino acids: An efficient synthesis of a key intermediate of diltiazem. J Org Chem 1996, 61, 24, 8586.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	28445	(2S)-2-amino-3,3-dimethylbutyric acid	C₆H₁₃NO₂	详情	详情
(VIII)	62436	(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one	C₁₆H₁₅NO₃S	详情	详情
(XXXIII)	63413	(6-bromo-3-pyridinyl)(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)methanone	C₁₃H₁₅BrN₂O₃	详情	详情
(XXXIV)	62452	2-(4-methoxyphenyl)-4-oxo-4,5-dihydro-1,5-benzothiazepin-3-yl acetate	C₁₈H₁₅NO₄S	详情	详情
(XXXV)	62453	2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione	C₁₆H₁₃NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Alkylation of the lactam N of thiazepinone (I) with 2-(dimethylamino)ethyl chloride (II) in the presence of K2CO3 or under phase-transfer conditions gave thiazeinone (III). Subsequent esterification of (III) with acetic anhydride furnished the title compound. Alternatively, diltiazem has been prepared by acetylation of thiazeinone (I) with Ac2O to yield the lactam acetate ester (IV), which is then alkylated with chloride (II) under phase-transfer conditions

参考文献中间体

合成目标

【1】 Coffen, D.L.; Madan, P.B.; Schwartz, A. (F. Hoffmann-La Roche AG); Process for the preparation of optically pure aminophenylthio- and aminonaphthalenylthio-propanoic acids. EP 0343474 .
【2】 Honma, T.; Igarashi, K. (Shionogi & Co. Ltd.); Process for production of diltiazem hydrochloride. US 4552695 .
【3】 Murthy, K.; Weeratunga, G.; Burchat, A. (ACIC (Canada) Inc.); Method for the manufacture of benzothiazepine derivs.. WO 9638429 .
【4】 Piselli, F.L.; Boschi, P.; Navoni, C.; A process for the preparation of diltiazem. EP 0594101 .
【5】 Bhushan, L.B.; Jayachandran, B.E.; Bhushan, L.V.; Thottappillil, R. (Council of Scientific and Industrial Research); Process for preparing diltiazem. US 5869697 .
【6】 Hytonen, M. (Orion Corporation); Process for the manufacture of diltiazem. EP 0728751; JP 1996253464; US 5644054 .
【7】 Hulshof, L.A.; Kuilman, T.; Process for preparing 1,5-benzothiazepin derivs.. EP 0450705 .
【8】 Manghisi, E.; Cascio, G. (Lusofarmaco); Process for the optical resolution of the dl-alpha-hydroxy-3-(4-methoxyphenyl)-3-(2-aminophenylthio)propionic acid. US 4533748 .
【9】 Simonovitch, H.; Hoffmann, T.; Sassoon, S. (Abic, Ltd.); A process for the preparation of benzothiazepin derivs.. EP 0158303 .
【10】 Hytonen, M. (Orion Corporation); Method for the preparation of pharmaceutically active benzothiazepine derivs.. EP 0702009 .
【11】 Manghisi, E.; Perego, B.; A process for the preparation of diltiazem. WO 9210485 .

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)	62436	(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one		C₁₆H₁₅NO₃S	详情	详情
(II)	11907	Dimethylaminoethyl chloride; 2-Dimethylaminoethyl chloride; 2-Chloro-N,N-dimethyl-1-ethanamine; N-(2-Chloroethyl)-N,N-dimethylamine	107-99-3	C₄H₁₀ClN	详情	详情
(III)	62488	(2S,3S)-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one		C₂₀H₂₄N₂O₃S	详情	详情
(IV)	62452	2-(4-methoxyphenyl)-4-oxo-4,5-dihydro-1,5-benzothiazepin-3-yl acetate		C₁₈H₁₅NO₄S	详情	详情

Extended Information