N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide -Drug Synthesis Database

【结构式】

【分子编号】19591

【品名】N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide

【CA登记号】

【分子式】C₁₇H₁₅BrClNO₃S

【分子量】428.73374

【元素组成】C 47.63% H 3.53% Br 18.64% Cl 8.27% N 3.27% O 11.2% S 7.48%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XVI)

The alcohol (XV) was oxidized with 4-benzylpyridinium dichromate to the aldehyde (XVI). 3-(Tributylstannylmethyl)pyridine (XVIII), prepared from lithiated 3-picoline (XVII) and Bu3SnCl in the presence of HMPA, was coupled to bromotetrahydronaphthalene (XVI) under palladium catalysis to provide the pyridylmethyl derivative (XIX). Wittig reaction of (XIX) with phosphorane (IX) gave acrylate (XX), which was reduced with NaBH4 and CoCl2 to the tetrahydronaphthylpropionic ester (XXI). Finally, the ester group of (XXI) was hydrolyzed with NaOH in MeOH-H2O to give the title acid.

参考文献中间体

合成目标

【1】 Cimetière, B.; Dubuffet, T.; Landras, C.; Descombes, J.J.; Simonet, S.; Verbeuren, T.J.; Lavielle, G.; New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors. Bioorg Med Chem Lett 1998, 8, 11, 1381.
【2】 Lavielle, G.; Dubuffet, T.; Muller, O.; Laubie, M.; Verbeuren, T.; Simonet, S.; Descombes, J.-J. (ADIR et Cie.); 1,2,3,4-Tetrahydronaphthalene, chroman and thiochroman derivs. as antithrombotic agents. CA 2118102; EP 0648741; FR 2711139; JP 1995188155 .

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)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(XVI)	19591	N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide		C₁₇H₁₅BrClNO₃S	详情	详情
(XVII)	19592	(3-pyridinylmethyl)lithium		C₆H₆LiN	详情	详情
(XVIII)	19572	3-[(tributylstannyl)methyl]pyridine		C₁₈H₃₃NSn	详情	详情
(XIX)	19594	4-chloro-N-[5-formyl-7-(3-pyridinylmethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]benzenesulfonamide		C₂₃H₂₁ClN₂O₃S	详情	详情
(XX)	19595	methyl (E)-3-[6-[[(4-chlorophenyl)sulfonyl]amino]-3-(3-pyridinylmethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]-2-propenoate		C₂₆H₂₅ClN₂O₄S	详情	详情
(XXI)	19596	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-3-(3-pyridinylmethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate		C₂₆H₂₇ClN₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Bromination of the coumarin derivative (I) with Br2 in DMF afforded the bromo coumarin (II). Diels-Alder cycloaddition between bromo coumarin (II) and ethyl 3-(trimethylsilyl)propiolate (III) with concomitant decarboxylation furnished the tetrahydronaphthalene (IV). After desilylation of (IV) with trifluoroacetic acid, the resultant ester (V) was reduced to alcohol (VI) using the combination LiAlH4-AlCl3. Further oxidation of the alcohol function of (VI) to aldehyde (VII) was performed with 4-benzylpyridinium dichromate (BPDC) in CH2Cl2. Wittig reaction of aldehyde (VII) with methyl (triphenylphosphoranylidene)acetate produced the arylacrylate ester (VIII), which was then reduced to the saturated ester (IX) employing NaBH4 in the presence of CoCl2.

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.

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)	19586	4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide		C₁₅H₁₄ClNO₄S	详情	详情
(II)	19587	N-(3-bromo-2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)-4-chlorobenzenesulfonamide		C₁₅H₁₃BrClNO₄S	详情	详情
(III)	23898	ethyl 3-(trimethylsilyl)-2-propynoate	29394-58-9	C₈H₁₄O₂Si	详情	详情
(IV)	49920	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₂₂H₂₇BrClNO₄SSi	详情	详情
(V)	49921	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₁₉H₁₉BrClNO₄S	详情	详情
(VI)	19590	N-[7-bromo-5-(hydroxymethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide		C₁₇H₁₇BrClNO₃S	详情	详情
(VII)	19591	N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide		C₁₇H₁₅BrClNO₃S	详情	详情
(VIII)	49922	methyl (E)-3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate		C₂₀H₁₉BrClNO₄S	详情	详情
(IX)	49923	methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₀H₂₁BrClNO₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

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.

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)	19586	4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide		C₁₅H₁₄ClNO₄S	详情	详情
(II)	19587	N-(3-bromo-2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)-4-chlorobenzenesulfonamide		C₁₅H₁₃BrClNO₄S	详情	详情
(III)	23898	ethyl 3-(trimethylsilyl)-2-propynoate	29394-58-9	C₈H₁₄O₂Si	详情	详情
(IV)	49920	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₂₂H₂₇BrClNO₄SSi	详情	详情
(V)	49921	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₁₉H₁₉BrClNO₄S	详情	详情
(VI)	19590	N-[7-bromo-5-(hydroxymethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide		C₁₇H₁₇BrClNO₃S	详情	详情
(VII)	19591	N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide		C₁₇H₁₅BrClNO₃S	详情	详情
(VIII)	49922	methyl (E)-3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate		C₂₀H₁₉BrClNO₄S	详情	详情
(IX)	49923	methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₀H₂₁BrClNO₄S	详情	详情

Extended Information