methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate -Drug Synthesis Database

【结构式】

【分子编号】52244

【品名】methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate

【CA登记号】

【分子式】C₂₈H₃₅NO₅S

【分子量】497.65564

【元素组成】C 67.58% H 7.09% N 2.81% O 16.07% S 6.44%

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：(V)

5-Hydroxybenzothiophene-3-carboxylic acid (I) was esterified with acetic anhydride in pyridine to afford the 5-acetoxy derivative (II). Treatment of (II) with thionyl chloride produced acid chloride (III), which was condensed with the previously reported bicyclic amine (IV), yielding amide (V). The ester groups of (V) were finally hydrolyzed under basic conditions to furnish the target compound.

参考文献中间体

合成目标

【1】 Tsuri, T.; Honma, T.; Hiramatsu, Y.; Okada, T.; Hashizume, H.; Mitsumori, S.; Inagaki, M.; Arimura, A.; Yasui, K.; Asanuma, F.; Kishino, J.; Ohtani, M.; Bicyclo[2.2.1]heptane and 6,6-dimethylbicyclo[3.1.1]heptane derivatives: Orally active, potent, and selective prostaglandin D2 receptor antagonists. J Med Chem 1997, 40, 22, 3504.
【2】 Arimura, A.; Honma, T.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Benzothiophenecarboxamide derivs. and PGD2 antagonists comprising them. EP 0944614; JP 2000514824; US 6083974; WO 9825919 .
【3】 Arimura, A. (Shionogi & Co. Ltd.); Remedies for itching containing PGD2 antagonists. EP 1084711; WO 9962555 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	52240	5-hydroxy-1-benzothiophene-3-carboxylic acid	C₉H₆O₃S	详情	详情
(II)	52241	5-(acetyloxy)-1-benzothiophene-3-carboxylic acid	C₁₁H₈O₄S	详情	详情
(III)	52242	3-(chlorocarbonyl)-1-benzothiophen-5-yl acetate	C₁₁H₇ClO₃S	详情	详情
(IV)	52243	methyl (Z)-7-[(1R,2R,3S,5R)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate	C₁₇H₂₉NO₂	详情	详情
(V)	52244	methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate	C₂₈H₃₅NO₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XLVII)

Coupling of amino ester (XLIV) with carboxylic acid (IX) by means of EDC and HOBt produced the corresponding amide ester (XLV). In a related procedure, the analogous amino methyl ester (XLVI) was coupled with acid chloride (XV) to yield amide (XLVII). The title compound was then obtained by hydrolysis of the ethyl ester (XLV) with LiOH or by NaOH hydrolysis of diester (XLVII).

参考文献中间体

合成目标

【1】 Tsuri, T.; Honma, T.; Hiramatsu, Y.; Okada, T.; Hashizume, H.; Mitsumori, S.; Inagaki, M.; Arimura, A.; Yasui, K.; Asanuma, F.; Kishino, J.; Ohtani, M.; Bicyclo[2.2.1]heptane and 6,6-dimethylbicyclo[3.1.1]heptane derivatives: Orally active, potent, and selective prostaglandin D2 receptor antagonists. J Med Chem 1997, 40, 22, 3504.
【2】 Arimura, A.; Honma, T.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Benzothiophenecarboxamide derivs. and PGD2 antagonists comprising them. EP 0944614; JP 2000514824; US 6083974; WO 9825919 .
【3】 Cai, D.; Larsen, R.; Journet, M.; Campos, K. (Merck & Co., Inc.); Process for the preparation of PGD2 antagonist. WO 0232892 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	52240	5-hydroxy-1-benzothiophene-3-carboxylic acid	C₉H₆O₃S	详情	详情
(XV)	52242	3-(chlorocarbonyl)-1-benzothiophen-5-yl acetate	C₁₁H₇ClO₃S	详情	详情
(XLIV)	60688	ethyl (Z)-7-[(1R,2R,3S,5R)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate	C₁₈H₃₁NO₂	详情	详情
(XLV)	60689	ethyl (Z)-7-((1R,2R,3S,5R)-2-{[(5-hydroxy-1-benzothiophen-3-yl)carbonyl]amino}-6,6-dimethylbicyclo[3.1.1]hept-3-yl)-5-heptenoate	C₂₇H₃₅NO₄S	详情	详情
(XLVI)	52243	methyl (Z)-7-[(1R,2R,3S,5R)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate	C₁₇H₂₉NO₂	详情	详情
(XLVII)	52244	methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate	C₂₈H₃₅NO₅S	详情	详情

Extended Information