1,5-pentanediol -Drug Synthesis Database

【结构式】

【分子编号】15471

【品名】1,5-pentanediol

【CA登记号】111-29-5

【分子式】C₅H₁₂O₂

【分子量】104.14908

【元素组成】C 57.66% H 11.61% O 30.72%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(II)

The reaction of acryloyl chloride (I) with pentane-1,5-diol (II) by means of triethylamine and pyrogalol in hot benzene gives 1,5-pentamethylene diacrylate (III), which is condensed with tetrahydropapaverine (IV) in refluxing benzene to afford N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-bis(tetrahydropapaverine) (V). Finally, this compound is quaternized by treatment with methyl benzenesulfonate in acetonitrile.

参考文献中间体

合成目标

【1】 Dewar, G.H.; Dhar, N.C.; Sternlake, J.B.; Urwin, R.J.; Waigh, R.D. (Glaxo Wellcome Inc.); Quarternary ammonium compounds. DE 2655883; FR 2334359; JP 52077069; US 4179507 .
【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hillier, K.; Atracurium Besilate. Drugs Fut 1980, 5, 11, 541.

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)	11577	Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride	814-68-6	C₃H₃ClO	详情	详情
(II)	15471	1,5-pentanediol	111-29-5	C₅H₁₂O₂	详情	详情
(III)	15470	5-(acryloyloxy)pentyl acrylate; 1,6-Hexanediol Diacrylate	36840-85-4	C₁₁H₁₆O₄	详情	详情
(IV)	15468	1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether		C₂₀H₂₅NO₄	详情	详情
(V)	15473	5-([3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoyl]oxy)pentyl 3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoate		C₅₁H₆₆N₂O₁₂	详情	详情
(VI)	15474	methyl benzenesulfonate	80-18-2	C₇H₈O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The optical resolution of (±)-tetrahydropapaverine (I) with N-acetyl-L-leucine yields (R)-tetrahydropapaverine (II), which is condensed with 1,5-pentamethylene diacrylate (III) (obtained by esterification of 1,5-pentanediol (IV) with 3-bromopropionic acid by means of p-toluenesulfonic acid followed by dehydromination with triethylamine) in hot glacial acetic acid and treated with oxalic acid to afford the bis-tetrahydropapaverine derivative (VI). Finally, this compound is treated with aqueous Na2CO3 to eliminate the oxalic acid and then treated with methyl benezenesulfonate (VII) at room temperature. The resulting product is a 58:34:6 mixture of the (1R-cis, 1'R-cis)- (1R-cis, 1'R-trans)- and (1R-trans, 1'R-trans)-isomers, which is resolved by column chromatography over silica gel using an 80:20:5 mixture of dichloromethane methanol and methanesulfonic acid.

参考文献中间体

合成目标

【1】 Mealy, N.; Castaner, J.; Cisatracurium Besylate. Drugs Fut 1996, 21, 1, 14.
【2】 Hill, D.A.; Turner, G.L. (Glaxo Wellcome plc); Neuromuscular blocking agents. CH 683427; EP 0539470; FR 2665791; GB 2260763; JP 1993508648; JP 1998139763; US 5453510; WO 9200965 .

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)	15468	1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether		C₂₀H₂₅NO₄	详情	详情
(II)	15469	(1R)-1-(3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether; (1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline		C₂₀H₂₅NO₄	详情	详情
(III)	15470	5-(acryloyloxy)pentyl acrylate; 1,6-Hexanediol Diacrylate	36840-85-4	C₁₁H₁₆O₄	详情	详情
(IV)	15471	1,5-pentanediol	111-29-5	C₅H₁₂O₂	详情	详情
(V)	15472	3-Bromopropionic acid	590-92-1	C₃H₅BrO₂	详情	详情
(VI)	15473	5-([3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoyl]oxy)pentyl 3-[(1R)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]propanoate		C₅₁H₆₆N₂O₁₂	详情	详情
(VII)	15474	methyl benzenesulfonate	80-18-2	C₇H₈O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Mitsunobu coupling of 1,5-pentanediol (II) with two molecules of 4-hydroxybenzonitrile (I) in the presence of diisopropyl azodicarboxylate (DIAD) and triphenylphosphine afforded diether (III). Subsequent reduction of the nitrile groups of (III) using LiAlH4 gave the bis(benzylamine) derivative (IV), which was coupled with 3-cyanobenzenesulfonyl chloride (V) to provide sulfonamide (VI). The nitrile groups of (VI) were finally converted to the required bis amidino derivative by treatment with Weinreb reagent, prepared from trimethylaluminum and ammonium chloride.

参考文献中间体

合成目标

【1】 Burgess, L.; Rizzi, J.P. (Array BioPharma, Inc.); Cpds. which inhibit tryptase activity. WO 9924395 .

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)	25109	4-hydroxybenzonitrile	767-00-0	C₇H₅NO	详情	详情
(II)	15471	1,5-pentanediol	111-29-5	C₅H₁₂O₂	详情	详情
(III)	37312	4-[[5-(4-cyanophenoxy)pentyl]oxy]benzonitrile		C₁₉H₁₈N₂O₂	详情	详情
(IV)	37313	[4-([5-[4-(aminomethyl)phenoxy]pentyl]oxy)phenyl]methanamine; 4-([5-[4-(aminomethyl)phenoxy]pentyl]oxy)benzylamine		C₁₉H₂₆N₂O₂	详情	详情
(V)	37314	3-cyanobenzenesulfonyl chloride		C₇H₄ClNO₂S	详情	详情
(VI)	37315	3-cyano-N-[4-([5-[4-([[(3-cyanophenyl)sulfonyl]amino]methyl)phenoxy]pentyl]oxy)benzyl]benzenesulfonamide		C₃₃H₃₂N₄O₆S₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The target product can be obtained by condensation of trimethylhydroquinone (I) with diol (II) by means of phosphomolybdic acid in refluxing toluene followed by recrystallization from n-hexane/ethyl acetate.

参考文献中间体

合成目标

【1】 Satoh, T.; Miyataka, H.; Nishiki, M.; Hirano, T.; Kawasaki, N.; Antioxidative and 5-lipoxygenase inhibiting activities of novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives. Chem Pharm Bull 2001, 49, 2, 225.

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)	26357	2,3,5-trimethyl-1,4-benzenediol	700-13-0	C₉H₁₂O₂	详情	详情
(II)	15471	1,5-pentanediol	111-29-5	C₅H₁₂O₂	详情	详情

Extended Information