methyl 3-[(2-chloro-4-formylphenyl)sulfanyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】48173

【品名】methyl 3-[(2-chloro-4-formylphenyl)sulfanyl]propanoate

【CA登记号】

【分子式】C₁₁H₁₁ClO₃S

【分子量】258.72524

【元素组成】C 51.07% H 4.29% Cl 13.7% O 18.55% S 12.39%

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：(II)

Reaction of 3,4-dichlorobenzalzehyde (I) with methyl 3-mercaptopropionate in the presence of K2CO3 in hot DMF afforded the thioether (II). Subsequent condensation of (II) with malonic acid under Knoevenagel conditions produced the substituted cinnamic acid (III), which was further converted to the corresponding acid chloride (IV) upon treatment with oxalyl chloride and a catalytic amount of DMF. Coupling of acid chloride (IV) with N-acetylpiperazine (V) furnished amide (VI). Treatment of (VI) with potassium tert-butoxide caused the elimination of methyl acrylate, producing the potassium thiolate (VII). Thiolate (VII) was then condensed with 1-methyl-7-bromoindole (VIII) to give the title compound.

参考文献中间体

合成目标

【1】 Lynch, J.K.; Link, J.; Zhu, G.-D.; Boyd, S.A.; Winn, M.; Pei, Z.; Gunawardana, I.W.; Liu, G.; Xin, Z.; Jae, H.-S.; Freeman, J.C.; Von Geldern, T.; Staeger, M.A. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. US 6110922; WO 0039081 .
【2】 Jae, H.-S.; Pei, Z.; Staeger, M.A.; Gunawardana, I.W.; Winn, M.; Freeman, J.C.; Liu, G.; Link, J.; Boyd, S.A.; Zhu, G.-D.; Von Geldern, T.W.; Xin, Z.; Lynch, J.K.; Wang, S. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. WO 0059880 .

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)	18122	3,4-Dichlorobenzaldehyde	6287-38-3	C₇H₄Cl₂O	详情	详情
(II)	48173	methyl 3-[(2-chloro-4-formylphenyl)sulfanyl]propanoate		C₁₁H₁₁ClO₃S	详情	详情
(III)	48174	(E)-3-[3-chloro-4-[(3-methoxy-3-oxopropyl)sulfanyl]phenyl]-2-propenoic acid		C₁₃H₁₃ClO₄S	详情	详情
(IV)	48175	methyl 3-([2-chloro-4-[(E)-3-chloro-3-oxo-1-propenyl]phenyl]sulfanyl)propanoate		C₁₃H₁₂Cl₂O₃S	详情	详情
(V)	20674	N-Acetyl piperazine; 1-(1-piperazinyl)-1-ethanone	13889-98-0	C₆H₁₂N₂O	详情	详情
(VI)	48176	methyl 3-([4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorophenyl]sulfanyl)propanoate		C₁₉H₂₃ClN₂O₄S	详情	详情
(VII)	48177	potassium 4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorobenzenethiolate		C₁₅H₁₆ClKN₂O₂S	详情	详情
(VIII)	29521	5-bromo-1-methyl-1H-indole		C₉H₈BrN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Aromatic nucleophilic substitution of 3-chloro-4-fluorobenzaldehyde (I) with methyl 3-mercaptopropionate (II) yielded the mercapto aldehyde (III). This was subjected to Knoevenagel condensation with malonic acid to furnish the cinnamic acid derivative (IV), which was further converted to the corresponding acid chloride (V) by using oxalyl chloride. Condensation of acid chloride (V) with N-acetylpiperazine (VI) yielded the diacyl piperazine (VII). The protected benzenethiol of (VII) was released by treatment of the beta-mercaptopropionate (VII) with potassium tert-butoxide to give the potassium thiolate (VIII). Finally, Ullmann coupling of (VIII) with 6-iodobenzodioxan (IX) furnished the title compound.

参考文献中间体

合成目标

【1】 Liu, G.; Okasinski, O.F.; DeVries, P.; Mendoza, R.; Leitza, S.; Olejniczak, E.T.; von Geldern, T.W.; Huth, J.R.; Fesik, S.W.; Reilly, E.B.; Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties. J Med Chem 2001, 44, 8, 1202.
【2】 Jae, H.-S.; Pei, Z.; Staeger, M.A.; Gunawardana, I.W.; Winn, M.; Freeman, J.C.; Liu, G.; Link, J.; Boyd, S.A.; Zhu, G.-D.; Von Geldern, T.W.; Xin, Z.; Lynch, J.K.; Wang, S. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. WO 0059880 .

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)	49749	3-Chloro-4-fluorobenzaldehyde; 4-Fluoro-3-chlorobenzaldehyde	34328-61-5	C₇H₄ClFO	详情	详情
(II)	11418	methyl 3-sulfanylpropanoate; Methyl 3-mercaptopropionate	2935-90-2	C₄H₈O₂S	详情	详情
(III)	48173	methyl 3-[(2-chloro-4-formylphenyl)sulfanyl]propanoate		C₁₁H₁₁ClO₃S	详情	详情
(IV)	48174	(E)-3-[3-chloro-4-[(3-methoxy-3-oxopropyl)sulfanyl]phenyl]-2-propenoic acid		C₁₃H₁₃ClO₄S	详情	详情
(V)	48175	methyl 3-([2-chloro-4-[(E)-3-chloro-3-oxo-1-propenyl]phenyl]sulfanyl)propanoate		C₁₃H₁₂Cl₂O₃S	详情	详情
(VI)	20674	N-Acetyl piperazine; 1-(1-piperazinyl)-1-ethanone	13889-98-0	C₆H₁₂N₂O	详情	详情
(VII)	48176	methyl 3-([4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorophenyl]sulfanyl)propanoate		C₁₉H₂₃ClN₂O₄S	详情	详情
(VIII)	48177	potassium 4-[(E)-3-(4-acetyl-1-piperazinyl)-3-oxo-1-propenyl]-2-chlorobenzenethiolate		C₁₅H₁₆ClKN₂O₂S	详情	详情
(IX)	49750	3,4-Ethylenedioxyiodobenzene	57744-67-9	C₈H₇IO₂	详情	详情

Extended Information