methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-3-(hydroxymethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】49926

【品名】methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-3-(hydroxymethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate

【CA登记号】

【分子式】C₂₁H₂₄ClNO₅S

【分子量】437.944

【元素组成】C 57.59% H 5.52% Cl 8.1% N 3.2% O 18.27% S 7.32%

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：(XIII)

Heck reaction of aryl bromide (IX) with vinyl tributyltin (X) in the presence of palladium catalyst gave the vinyl tetrahydronaphthalene (XI), which was converted to the primary alcohol (XII) by means of hydroboration with borane in THF followed by oxidative treatment with H2O2 and NaOH. Reaction of alcohol (XII) with p-toluenesulfonyl chloride and Et3N produced the corresponding tosylate (XIII) (1). This was then condensed with 6-fluoro-3-(4-piperidinyl)benzisoxazole (XIV), yielding adduct (XV). Finally, basic hydrolysis of the ester group of (XIV) provided the title carboxylic acid.

参考文献中间体

合成目标

【1】 Cimetiere, B.; et al.; Discovery of new combined 5-HT2 and TP-receptor antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 57.
【2】 Verbeuren, T.; Simonet, S.; Descombes, J.-J.; Cimetiere, B.; Lavielle, G. (ADIR et Cie.); Benzenesulfonamide derivs., process for their preparation and pharmaceutical compsns. containing them. EP 1118610; FR 2803848; JP 2001226353 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	49923	methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₀H₂₁BrClNO₄S	详情	详情
(X)	24920	tributyl(vinyl)stannane；Tributylvinylstannane;Vinyltributylstannane	7486-35-3	C₁₄H₃₀Sn	详情	详情
(XI)	49924	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-3-vinyl-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₂H₂₄ClNO₄S	详情	详情
(XII)	49925	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-3-formyl-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₁H₂₂ClNO₅S	详情	详情
(XIII)	49926	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-3-(hydroxymethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate		C₂₁H₂₄ClNO₅S	详情	详情
(XIV)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole		C₁₂H₁₃FN₂O	详情	详情
(XV)	49964	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₃₄H₃₇ClFN₃O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Heck reaction of aryl bromide (IX) with vinyl tributyltin (X) in the presence of palladium catalyst gave the vinyl tetrahydronaphthalene (XI), which was subjected to oxidative double-bond cleavage to aldehyde (XII) using NaIO4 in the presence of a catalytic amount of OsO4. Aldehyde reduction with NaBH4 provided alcohol (XIII). This was then converted to the corresponding bromide (XIV) by treatment with carbon tetrabromide and triphenylphosphine.

参考文献中间体

合成目标

【1】 Cimetiere, B.; et al.; Discovery of new combined 5-HT2 and TP-receptor antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 57.
【2】 Verbeuren, T.; Simonet, S.; Descombes, J.-J.; Cimetiere, B.; Lavielle, G. (ADIR et Cie.); Benzenesulfonamide derivs., process for their preparation and pharmaceutical compsns. containing them. EP 1118610; FR 2803848; JP 2001226353 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	49923	methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₀H₂₁BrClNO₄S	详情	详情
(X)	24920	tributyl(vinyl)stannane；Tributylvinylstannane;Vinyltributylstannane	7486-35-3	C₁₄H₃₀Sn	详情	详情
(XI)	49924	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-3-vinyl-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₂H₂₄ClNO₄S	详情	详情
(XII)	49925	methyl 3-(6-[[(4-chlorophenyl)sulfonyl]amino]-3-formyl-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₁H₂₂ClNO₅S	详情	详情
(XIII)	49926	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-3-(hydroxymethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate		C₂₁H₂₄ClNO₅S	详情	详情
(XIV)	49927	methyl 3-(3-(bromomethyl)-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₁H₂₃BrClNO₄S	详情	详情

Extended Information