Allyltributyltin; Tributyl-2-propenylstannane -Drug Synthesis Database

【结构式】

【分子编号】40599

【品名】Allyltributyltin; Tributyl-2-propenylstannane

【CA登记号】24850-33-7

【分子式】C₁₅H₃₂Sn

【分子量】331.12908

【元素组成】C 54.41% H 9.74% Sn 35.85%

与该中间体有关的原料药合成路线共 8 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6 合成路线7 合成路线8

合成路线1

该中间体在本合成路线中的序号：(III)

The reaction of the chiral oxazolidinone (I) with (Boc)2O gives the N-protected oxazolidinone (II), which is irradiated with UV light in acetonitrile in the presence of Bu3Sn-SnBu3 and the allylstannane (III) to yield the chiral 5-allyloxazolidinone (IV). Ring cleavage of (IV) by means of Cs2CO3 in methanol affords the N-protected aminoalcohol (V), which is treated with Ms-Cl and TEA in dichloromethane to provide the mesylate (VI). Epimerization of the O-Ms group of (VI) by means of Cs-OAc and 18-crown-6 in refluxing benzene gives the epimeric acetate (VII), which is hydrolyzed with K2CO3 in methanol to yield the N-protected aminoalcohol (VIII). The O-methylation of (VIII) by means of Me-I and Tl-OEt in THF affords the methyl ether (IX), which is N-methylated by means of Me-I and NaH in THF to provide the N-methyl carbamate (X). Finally, the terminal double bond of (X) is oxidated with RuCl3 and NaIO4 in CCl4/acetonitrile/water to furnish the target intermediate, the carboxylic acid (XI) (see scheme no. 149507a, intermediate (VIII)).

参考文献中间体

合成目标

【1】 Kano, S.; et al.; Highly diastereoselective synthesis of N-Boc dolaisoleuine, unusual amino acid in dolastatin 10. Heterocycles 1990, 31, 9, 1597.

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)	54637	(4S)-4-(sec-butyl)-5-(phenylsulfanyl)-1,3-oxazolidin-2-one		C₁₃H₁₇NO₂S	详情	详情
(II)	54638	tert-butyl (4S)-4-(sec-butyl)-2-oxo-5-(phenylsulfanyl)-1,3-oxazolidine-3-carboxylate		C₁₈H₂₅NO₄S	详情	详情
(III)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(IV)	54639	tert-butyl (4S,5S)-5-allyl-4-(sec-butyl)-2-oxo-1,3-oxazolidine-3-carboxylate		C₁₅H₂₅NO₄	详情	详情
(V)	54640	tert-butyl (1S,2S)-1-(sec-butyl)-2-hydroxy-4-pentenylcarbamate		C₁₄H₂₇NO₃	详情	详情
(VI)	54641	(1S)-1-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-methylbutyl}-3-butenyl methanesulfonate		C₁₅H₂₉NO₅S	详情	详情
(VII)	54642	(1R)-1-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-methylbutyl}-3-butenyl acetate		C₁₆H₂₉NO₄	详情	详情
(VIII)	54597	tert-butyl (1S,2R)-1-(sec-butyl)-2-hydroxy-4-pentenylcarbamate		C₁₄H₂₇NO₃	详情	详情
(IX)	54643	tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenylcarbamate		C₁₅H₂₉NO₃	详情	详情
(X)	54598	tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenyl(methyl)carbamate		C₁₆H₃₁NO₃	详情	详情
(XI)	54599	(3R,4S)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-methoxy-5-methylheptanoic acid		C₁₅H₂₉NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Synthesis of thiazole intermediate (IX): The reaction of 2-methylthiazole-4-carbaldehyde (I) with triphenylphosphorane (II) in refluxing benzene gives 2-methyl-3-(2-methyl-4-thiazolyl)-2-propenal (III), which is enantioselectively allylated with ally(tributyl)stannane (IV) catalyzed by (S)(-)-BINOL and Ti(O-iPr)4 in dichloromethane to yield the chiral homoallyl alcohol (V). The reaction of (V) with acetic anhydride TEA and DMAP in dichloromethane affords the acetate (VI), which is oxidized at its terminal double bond with OsO4 and NaIO4 to provide the aldehyde (VII). Finally, this compound is condensed with triphenylphosphorane (VIII) to give the desired thiazole intermediate (IX).

参考文献中间体

合成目标

【1】 Meng, D.; et al.; Total syntheses of epothilones A and B. J Am Chem Soc 1997, 119, 42, 10073.

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)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(II)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(III)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(IV)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(V)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(VI)	44530	(1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₇NO₂S	详情	详情
(VII)	44531	(1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate		C₁₂H₁₅NO₃S	详情	详情
(VIII)	44532	(iodomethylene)(triphenyl)phosphorane		C₁₉H₁₆IP	详情	详情
(IX)	44493	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₆INO₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Synthesis of thiazole intermediate (IX): The reaction of 2-methylthiazole-4-carbaldehyde (I) with triphenylphosphorane (II) in refluxing benzene gives 2-methyl-3-(2-methyl-4-thiazolyl)-2-propenal (III), which is enantioselectively allylated with ally(tributyl)stannane (IV) and catalyzed by (S)-(-)-BINOL and Ti(O-iPr)4 in dichloromethane to yield the chiral homoallyl alcohol (V). The reaction of (V) with acetic anhydride TEA and DMAP in dichloromethane affords the acetate (VI), which is oxidized at its terminal double bond with OsO4 and NaIO4 to provide the aldehyde (VII). Finally, this compound is condensed with triphenylphosphorane (VIII) to gives the desired thiazole intermediate (IX).

参考文献中间体

合成目标

【1】 Meng, D.; et al.; Total syntheses of epothilones A and B. J Am Chem Soc 1997, 119, 42, 10073.
【2】 Bertinato, P.; Danishefsky, S.J.; Su, D.-S.; Kamenecka, T.; Meng, D.F.; Sorensen, E.J.; Savin, K.A.; Chou, T.-C.; Balog, A. (Sloan-Kettering Institute); Synthesis of epothilones, intermediates thereto, analogues and uses thereof. JP 2001507716; US 6242469; WO 9901124 .

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)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(II)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(III)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(IV)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(V)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(VI)	44530	(1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₇NO₂S	详情	详情
(VII)	44531	(1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate		C₁₂H₁₅NO₃S	详情	详情
(VIII)	42754	(1-iodoethylidene)(triphenyl)phosphorane		C₂₀H₁₈IP	详情	详情
(IX)	46125	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl acetate		C₁₄H₁₈INO₂S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Meng, D.; et al.; Total syntheses of epothilones A and B. J Am Chem Soc 1997, 119, 42, 10073.

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)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(II)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(III)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(IV)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(V)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(VI)	44530	(1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₇NO₂S	详情	详情
(VII)	44531	(1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate		C₁₂H₁₅NO₃S	详情	详情
(VIII)	42754	(1-iodoethylidene)(triphenyl)phosphorane		C₂₀H₁₈IP	详情	详情
(IX)	46125	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl acetate		C₁₄H₁₈INO₂S	详情	详情

合成路线5

该中间体在本合成路线中的序号：(XIII)

The Stille coupling of the benzodioxanone (XII) with allyltributyltin (XIII) by means of trifurylphosphine (TFP) and Pd2(dba)3 gives the 6-allylsalicylic acid (XIV), which is esterified with the intermediate (XI) by means of DEAD and PPH3 in ethyl ether to yield the ester (XV). Hydrolysis of the lactol group of (XV) with Ac-OH affords the carbaldehyde (XVI), which is condensed with the phosphorane (XVII) to provide the unsaturated ester (XVIII). The silylation of the free OH groups of (XVIII) with Tbdms-OTf and lutidine gives the protected compound (XIX), which is submitted to a rig closing metathesis reaction catalyzed by a Ru catalyst in dichloromethane to yield the macrolactone (XX). The selective hydrolysis of the methyl ester group of (XX) by treatment with (Bu3Sn)2O in refluxing toluene affords the unsaturated carboxylic acid (XXI), which is treated with DPPA in refluxing benzene to provide the corresponding isocyanate (XXII). The reaction of the isocyanate group of (XXII) with (1Z,3Z)-hexadienyl cuprate, prepared in situ by reaction of Et-Li, CuBr/Me2S and acetylene, gives the silylated heptadienamide (XXIII), along with some pentanamide and nonatrienamide derivatives that are separated by chromatography. Finally, compound (XXIII) is desilylated by means of HF and pyridine in THF to provide the target salicylhalamide A.

参考文献中间体

合成目标

【1】 Bauer, M.; Maier, M.E.; Synthesis of the core structure of salicylihalamide A by intramolecular Suzuki reaction. Org Lett 2002, 4, 13, 2205.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	56942	(4S,6R)-2-methoxy-6-[(1S)-1-methyl-3-butenyl]tetrahydro-2H-pyran-4-ol		C₁₁H₂₀O₃	详情	详情
(XII)	56943	2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-5-yl trifluoromethanesulfonate		C₁₁H₉F₃O₆S	详情	详情
(XIII)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(XIV)	56944	2-allyl-6-hydroxybenzoic acid		C₁₀H₁₀O₃	详情	详情
(XV)	56945	(4R,6R)-2-methoxy-6-[(1S)-1-methyl-3-butenyl]tetrahydro-2H-pyran-4-yl 2-allyl-6-hydroxybenzoate		C₂₁H₂₈O₅	详情	详情
(XVI)	56946	(1R,3R,4S)-3-hydroxy-4-methyl-1-(2-oxoethyl)-6-heptenyl 2-allyl-6-hydroxybenzoate		C₂₀H₂₆O₅	详情	详情
(XVII)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(XVIII)	56947	(1S,3R,4S)-3-hydroxy-1-[(E)-4-methoxy-4-oxo-2-butenyl]-4-methyl-6-heptenyl 2-allyl-6-hydroxybenzoate		C₂₃H₃₀O₆	详情	详情
(XIX)	56948	(1S,3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-[(E)-4-methoxy-4-oxo-2-butenyl]-4-methyl-6-heptenyl 2-allyl-6-{[tert-butyl(dimethyl)silyl]oxy}benzoate		C₃₅H₅₈O₆Si₂	详情	详情
(XX)	56949	methyl (E)-4-((3S,5R,6S)-5,14-bis{[tert-butyl(dimethyl)silyl]oxy}-6-methyl-1-oxo-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-3-yl)-2-butenoate		C₃₃H₅₄O₆Si₂	详情	详情
(XXI)	56950	(E)-4-((3S,5R,6S)-5,14-bis{[tert-butyl(dimethyl)silyl]oxy}-6-methyl-1-oxo-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-3-yl)-2-butenoic acid		C₃₂H₅₂O₆Si₂	详情	详情
(XXII)	56951	(3S,5R,6S)-5,14-bis{[tert-butyl(dimethyl)silyl]oxy}-3-[(E)-3-isocyanato-2-propenyl]-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one		C₃₂H₅₁NO₅Si₂	详情	详情
(XXIII)	56952	(2Z,4Z)-N-[(E)-3-((3S,5R,6S)-5,14-bis{[tert-butyl(dimethyl)silyl]oxy}-6-methyl-1-oxo-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-3-yl)-1-propenyl]-2,4-heptadienamide		C₃₈H₆₁NO₅Si₂	详情	详情

合成路线6

该中间体在本合成路线中的序号：(II)

The intermediate 6(S)-hydroxy-8-nonenoic acid methyl ester (III) has been obtained by enantioselective allylation of 6-oxohexanoic acid methyl ester (I) with allyltributylstannane (II) catalyzed by the chiral catalyst (R)-BINOL/Ti(O-iPr)4 in refluxing dichloromethane (other BINOL/metal catalysts have also been studied).

参考文献中间体

合成目标

【1】 Zimmer, R.; et al.; Enantioselective synthesis of (S)- and (R)-6-hydroxy-8-nonene-carboxylates by asymmetric catalysis: A formal synthesis of (R)-alpha-lipoic acid and its (S)-antipode. Tetrahedron Asymmetry 2000, 11, 4, 879.

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)	58067	Methyl 6-oxohexanoate		C₇H₁₂O₃	详情	详情
(II)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(III)	57996	methyl (6S)-6-hydroxy-8-nonenoate		C₁₀H₁₈O₃	详情	详情

合成路线7

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Meng, D.; et al.; Total syntheses of epothilones A and B. J Am Chem Soc 1997, 119, 42, 10073.

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)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(II)	39940	2-(triphenylphosphoranylidene)propanal		C₂₁H₁₉OP	详情	详情
(III)	44456	(E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal		C₈H₉NOS	详情	详情
(IV)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(V)	43171	(1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol		C₁₁H₁₅NOS	详情	详情
(VI)	44530	(1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₇NO₂S	详情	详情
(VII)	44531	(1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate		C₁₂H₁₅NO₃S	详情	详情
(VIII)	44532	(iodomethylene)(triphenyl)phosphorane		C₁₉H₁₆IP	详情	详情
(IX)	44493	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate		C₁₃H₁₆INO₂S	详情	详情

合成路线8

该中间体在本合成路线中的序号：(VII)

Synthesis of the perhydroindole intermediate (XIII): The alkylation of the N-protected glutamate (I) with allyl bromide (II) by means of LiHMDS in THF gives the protected chiral allyl glutamate (III) (1), which is cyclized by means of TFA in dichloromethane to yield the pyroglutamate (IV). The reduction of (IV) with LiHBEt3 in THF affords the hydroxy compound (V), which is treated with Ac2O and DMAP in dichloromethane to provide the expected hemiaminal derivative (VI). The reaction of (VI) with allyl tributylstannane (VII) by means of BF3/Et2O in toluene gives the diallyl pyrrolidine (VIII), which is submitted to a ring closure by olefin metathesis using a Grubbs Ru catalyst in dichloromethane to yield the hexahydroindole derivative (IX). The reaction of (IX) with mCPBA in dichloromethane affords the epoxide (X), which is hydrolyzed with TFA to yield the dihydroxy compound (XI). The reaction of (XI) with Mom-Cl and DIEA in dichloromethane provides the bis mom ether (XII), which is treated with H2 over Pd/C in methanol to yield the desired perhydroindole intermediate (XIII) (2).

参考文献中间体

合成目标

【1】 Hanessian, S.; Margarita, R.; 1,3-Asymmetric induction in dianionic allylation reactions of amino acid derivatives-synthesis of functionally useful enantiopure glutamates, pipecolates and pyroglutamates. Tetrahedron Lett 1998, 39, 33, 5887.
【2】 Hanessian, S.; Margarita, R.; Hall, A.; Johnstone, S.; Tremblay, M.; Parlanti, L.; Total synthesis and structural confirmation of the marine natural product Dysinosin A: A novel inhibitor of thrombin and Factor VIIa. J Am Chem Soc 2002, 124, 45, 13342.

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)	64903	dimethyl 2-({[(phenylmethyl)oxy]carbonyl}amino)pentanedioate		C₁₅H₁₉NO₆	详情	详情
(II)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(III)	64904	dimethyl 2-({[(phenylmethyl)oxy]carbonyl}amino)-4-(2-propenyl)pentanedioate		C₁₈H₂₃NO₆	详情	详情
(IV)	64905	2-methyl 1-(phenylmethyl) 5-oxo-4-(2-propenyl)-1,2-pyrrolidinedicarboxylate		C₁₇H₁₉NO₅	详情	详情
(V)	64906	2-methyl 1-(phenylmethyl) 5-hydroxy-4-(2-propenyl)-1,2-pyrrolidinedicarboxylate		C₁₇H₂₁NO₅	详情	详情
(VI)	64907	2-methyl 1-(phenylmethyl) 5-(acetyloxy)-4-(2-propenyl)-1,2-pyrrolidinedicarboxylate		C₁₉H₂₃NO₆	详情	详情
(VII)	40599	Allyltributyltin; Tributyl-2-propenylstannane	24850-33-7	C₁₅H₃₂Sn	详情	详情
(VIII)	64908	2-methyl 1-(phenylmethyl) 4,5-di(2-propenyl)-1,2-pyrrolidinedicarboxylate		C₂₀H₂₅NO₄	详情	详情
(IX)	64909	2-methyl 1-(phenylmethyl) 2,3,3a,4,7,7a-hexahydro-1H-indole-1,2-dicarboxylate		C₁₈H₂₁NO₄	详情	详情
(X)	64910	4-methyl 3-(phenylmethyl) octahydro-3H-oxireno[2,3-f]indole-3,4-dicarboxylate		C₁₈H₂₁NO₅	详情	详情
(XI)	64911	2-methyl 1-(phenylmethyl) 5,6-dihydroxyoctahydro-1H-indole-1,2-dicarboxylate		C₁₈H₂₃NO₆	详情	详情
(XII)	64912	2-methyl 1-(phenylmethyl) 5,6-bis{[(methyloxy)methyl]oxy}octahydro-1H-indole-1,2-dicarboxylate		C₂₂H₃₁NO₈	详情	详情
(XIII)	64913	methyl 5,6-bis{[(methyloxy)methyl]oxy}octahydro-1H-indole-2-carboxylate		C₁₄H₂₅NO₆	详情	详情

Extended Information