benzylhydrosulfide; phenylmethanethiol -Drug Synthesis Database

【结构式】

【分子编号】21110

【品名】benzylhydrosulfide; phenylmethanethiol

【CA登记号】100-53-8

【分子式】C₇H₈S

【分子量】124.20652

【元素组成】C 67.69% H 6.49% S 25.82%

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：(III)

4-(Aminomethyl)piperidine (I) was protected as the benzylideneimine (III) by condensation with benzaldehyde (II). Further acylation of (III) at the secondary amino group by treatment with di-tert--butyl dicarbonate gave, after acid hydrolysis of the imine, the N-Boc-piperidine (IV). The benzoic acid derivative (V) was activated as the mixed anhydride by treatment with ethyl chloroformate and triethylamine, and subsequently condensed with amine (IV) to provide the corresponding amide (VI). Then, the N-tert-butoxycarbonyl group was eliminated with HCl to give the piperidine (VII), which was finally alkylated with halide (VIII) in the presence of K2CO3 in DMF to furnish the title compound).

参考文献中间体

合成目标

【1】 Baker, S.R.; et al.; Synthesis and pharmacological evaluation of benzamides as selective 5-HT4 receptor agonists. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abs P 270.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(A)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(I)	19349	4-piperidinylmethylamine; 4-piperidinylmethanamine; 4-(Aminomethyl)piperidine	7144-05-0	C₆H₁₄N₂	详情	详情
(II)	19351	N-[(E)-benzylidene]-N-(4-piperidinylmethyl)amine; N-[(E)-benzylidene](4-piperidinyl)methanamine		C₁₃H₁₈N₂	详情	详情
(III)	21110	benzylhydrosulfide; phenylmethanethiol	100-53-8	C₇H₈S	详情	详情
(IV)	21111	benzyl(3-chloropropyl)dioxo-lambda(6)-sulfane; benzyl 3-chloropropyl sulfone		C₁₀H₁₃ClO₂S	详情	详情
(V)	21112	[1-[3-(benzylsulfonyl)propyl]-4-piperidinyl]methylamine; [1-[3-(benzylsulfonyl)propyl]-4-piperidinyl]methanamine		C₁₆H₂₆N₂O₂S	详情	详情
(VI)	12419	4-Amino-5-chloro-2-methoxybenzoic acid	7206-70-4	C₈H₈ClNO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The esterification of 2-nitroterephthalic acid (I) with isopropanol by means of dry HCl gives the corresponding dusoproyl ester (II), which by reaction with benzylmercaptane by means of NaH in DMF yields diisopropyl 2-benzylthioterephthalate (III). This compound is hydrolyzed with KOH in refluxing methanol affording the correspon-ding acid (IV), which is converted into its diacid chloride (V) by treatment with refluxing SOCl2. The cyclization of (V) with AlCl3 in methylene chloride - nitromethane affords 6,11-dihydrodibenzo[b]thiepin-11-one-3-carbonyl chloride (VI), which is treated with diazomethane in ether - methylene chloride to yield the 3-diazoacetyl derivative (VII). The Arndt-Eister reaction of (VII) with silver benzoate in refluxing methanol affords methyl 6,11-dihydrodibenzo[b,e]thiepin-11-one-3-acetate (VIII), which is finally hydrolyzed with KOH in refluxing methanol.

参考文献中间体

合成目标

【1】 Castañer, J.; Leeson, P.; Tiopinac. Drugs Fut 1978, 3, 12, 896.
【2】 Ackrell, J. (Syntex (USA), Inc.); 6,11-Dihydrodibenzothiepin-11-ones, compositions and uses thereof. US 4000308 .

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)	39919	2-nitroterephthalic acid	610-29-7	C₈H₅NO₆	详情	详情
(II)	39920	diisopropyl 2-nitroterephthalate		C₁₄H₁₇NO₆	详情	详情
(III)	21110	benzylhydrosulfide; phenylmethanethiol	100-53-8	C₇H₈S	详情	详情
(IV)	39921	diisopropyl 2-(benzylsulfanyl)terephthalate		C₂₁H₂₄O₄S	详情	详情
(V)	39922	2-(benzylsulfanyl)terephthalic acid		C₁₅H₁₂O₄S	详情	详情
(VI)	39923	3-(benzylsulfanyl)benzoyl chloride		C₁₄H₁₁ClOS	详情	详情
(VII)	39924	11-oxo-6,11-dihydrodibenzo[b,e]thiepine-3-carbonyl chloride		C₁₅H₉ClO₂S	详情	详情
(VIII)	39925	3-(2-diazoacetyl)dibenzo[b,e]thiepin-11(6H)-one		C₁₆H₁₀N₂O₂S	详情	详情
(IX)	39926	methyl 2-(11-oxo-6,11-dihydrodibenzo[b,e]thiepin-3-yl)acetate		C₁₇H₁₄O₃S	详情	详情

Extended Information