3-[(tributylstannyl)methyl]pyridine -Drug Synthesis Database

【结构式】

【分子编号】19572

【品名】3-[(tributylstannyl)methyl]pyridine

【CA登记号】

【分子式】C₁₈H₃₃NSn

【分子量】382.17676

【元素组成】C 56.57% H 8.7% N 3.66% Sn 31.06%

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：(XVIII)

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：(XVIII)

Then group of (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 SmI2 or 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
(XV)	19611	N-[7-bromo-5-(hydroxymethyl)-6-propyl-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide		C₂₀H₂₃BrClNO₃S	详情	详情
(XVI)	19612	N-(7-bromo-5-formyl-6-propyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide		C₂₀H₂₁BrClNO₃S	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)	19615	4-chloro-N-[5-formyl-6-propyl-7-(3-pyridinylmethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]benzenesulfonamide		C₂₆H₂₇ClN₂O₃S	详情	详情
(XX)	19616	methyl (E)-3-[6-[[(4-chlorophenyl)sulfonyl]amino]-2-propyl-3-(3-pyridinylmethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]-2-propenoate		C₂₉H₃₁ClN₂O₄S	详情	详情
(XXI)	19617	methyl 3-[6-[[(4-chlorophenyl)sulfonyl]amino]-2-propyl-3-(3-pyridinylmethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]propanoate		C₂₉H₃₃ClN₂O₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

2-Iodo-6-(4-chlorophenylsulfonyl)amino-5,6,7,8-tetrahydro-naphthyl-1-carbaldehyde (I) was coupled with 3-(tributylstannyl-methyl)pyridine (II) in the presence of Pd(PPh3)4 in N-methylpyrrolidine (NMP) at 110 C to afford the pyridinylmethyl derivative (III). Subsequent coupling of (VI) with (4-carboxybutyl)triphenylphosphonium chloride (IV) in the presence of potassium tert-butoxide in THF at low temperature provided a mixture of E and Z hexenoic acids (V), from which the target (E) isomer was isolated by column chromatography.

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.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	19571	4-chloro-N-(5-formyl-6-iodo-1,2,3,4-tetrahydro-2-naphthalenyl)benzenesulfonamide	C₁₇H₁₅ClINO₃S	详情	详情
(II)	19572	3-[(tributylstannyl)methyl]pyridine	C₁₈H₃₃NSn	详情	详情
(III)	19573	4-chloro-N-[5-formyl-6-(3-pyridinylmethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]benzenesulfonamide	C₂₃H₂₁ClN₂O₃S	详情	详情
(IV)	19574	(4-carboxybutyl)(triphenyl)phosphonium chloride	C₂₃H₂₄ClO₂P	详情	详情
(V)	19575	(E)-6-[6-[[(4-chlorophenyl)sulfonyl]amino]-2-(3-pyridinylmethyl)-5,6,7,8-tetrahydro-1-naphthalenyl]-5-hexenoic acid	C₂₈H₂₉ClN₂O₄S	详情	详情

Extended Information