ethyl 2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetate -Drug Synthesis Database

【结构式】

【分子编号】68516

【品名】ethyl 2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetate

【CA登记号】　

【分子式】C₂₈H₃₉NO₅S₂

【分子量】533.753

【元素组成】C 63.01% H 7.36% N 2.62% O 14.99% S 12.01%

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：(III)

Condensation of the 1,5-benzothiazepin-8-ol derivative (I) with ethyl bromoacetate (II) in the presence of Bu4NBr and Na2CO3 in refluxing acetonitrile yields ethyl ester (III), which is then hydrolyzed with NaOH in EtOH to give the corresponding acid (IV). Subsequent coupling of carboxylic acid (IV) with (R)-2-phenylglycine methyl ester hydrochloride (V) using TBTU and DIEA in CH2Cl2 followed by hydrolysis of the resultant methyl ester (VI) with NaOH in MeOH produces the N-acyl amino acid (VII). After coupling of acid (VII) with tert-butyl glycinate (VIII), using the same procedure as above, the resulting tert-butyl ester (IX) is finally cleaved using TFA in CH2Cl2 .

参考文献中间体

合成目标

【1】 Starke, I., Blomberg, D., Dahlstrom, M. (AstraZeneca AB; AstraZeneca plc). Chemical compounds. EP 1345918, JP 2004196815, JP 2004516285, US 2004067933, US 7192945, WO 2002050051.

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)	68515	3,3-dibutyl-8-hydroxy-7-(methylthio)-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine 1,1-dioxide		C₂₄H₃₃NO₃S₂	详情	详情
(II)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	68516	ethyl 2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetate		C₂₈H₃₉NO₅S₂	详情	详情
(IV)	68517	2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetic acid		C₂₆H₃₅NO₅S₂	详情	详情
(V)	68518	(R)-2-phenylglycine methyl ester hydrochloride		C₉H₁₁NO₂.HCl	详情	详情
(VI)	68519	(R)-methyl 2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetate		C₃₅H₄₄N₂O₆S₂	详情	详情
(VII)	68520	(R)-2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetic acid		C₃₄H₄₂N₂O₆S₂	详情	详情
(VIII)	27841	tert-butyl 2-aminoacetate;tert-butyl glycinate;Glycine tert-butyl ester	6456-74-2	C₆H₁₃NO₂	详情	详情
(IX)	68521	(R)-tert-butyl 2-(2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetamido)acetate		C₄₀H₅₃N₃O₇S₂	详情	详情

Extended Information