[(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate -Drug Synthesis Database

【结构式】

【分子编号】33832

【品名】[(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate

【CA登记号】

【分子式】C₂₆H₂₁BrO₇

【分子量】525.35254

【元素组成】C 59.44% H 4.03% Br 15.21% O 21.32%

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：(XIII)

The silylation of 1,2,4-triazole-3-carboxylic acid methyl ester (VII) with hexamethyldisylazane (HMDS) gives 1-(trimethylsilyl)-1,2,4-triazole-3-carboxylic acid methyl ester (XII), which is condensed with 2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl bromide (XIII) by means of PNPP at 160 C to afford the previously described intermediate 1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxylic acid methyl ester (XI).

参考文献中间体

合成目标

【1】 Laguna, N; Robins, R.K.; Witkowski, J.T. (ICN Pharmaceuticals, Inc.); 1,2,4-Triazole nucleosides. DE 2220246; US 3798209 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	33827	methyl 1H-1,2,4-triazole-3-carboxylate	4928-88-5	C₄H₅N₃O₂	详情	详情
(XI)	33830	methyl 1-[(2R,3R,4R,5R)-3,4-bis(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-2-furanyl]-1H-1,2,4-triazole-3-carboxylate		C₃₀H₂₅N₃O₉	详情	详情
(XII)	33831	methyl 1-(trimethylsilyl)-1H-1,2,4-triazole-3-carboxylate		C₇H₁₃N₃O₂Si	详情	详情
(XIII)	33832	[(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate		C₂₆H₂₁BrO₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Condensation of 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide (X) with diaminomaleonitrile (XI) yields the ribofuranosyl diamine (XII), which is alternatively prepared by N-protection of diamine (XI) with TMSCl in the presence of HMDS in refluxing acetonitrile and subsequent coupling of the obtained bis(silylamine) (XIII) with the D-ribofuranosyl acetate (XIV) by means of TMSOTf in CH2Cl2. Cyclization of diamine (XII) with HC(OEt)3 in the presence of NaOMe in anisole affords the 4,5-dicyanoimidazole derivative (XV), which undergoes regioselective addition of NaOMe in MeOH to give imidate (XVI). Finally, Hofmann rearrangement of imidate (XVI) with NaOCl in the presence of NaOH yields imidazolecarbonitrile (V) .
Alternatively, formylation of diaminomaleonitrile (XI) with HCOOH in benzene leads to N-formyldiaminomaleonitrile (XVII) , which is then silylated with TMSCl in the presence of HMDS to yield the protected amine (XVIII). Finally, amine (XVIII) is condensed with the ribofuranosyl acetate (XIV) in the presence of TMSOTf in CH2Cl2 to give compound (XIX), which undergoes cyclization using AcOH in refluxing benzene yielding nitrile (XV) .

参考文献中间体

合成目标

【1】 Ferris, J.P., Devadas, B., Huang, C.H., Ren, W.Y. Novel synthesis of 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide and 5-amino-1-(beta-D-ribopyranosyl)imidazole-4-carboxamide. J Org Chem 1985, 50(6): 747-54.
【2】 Ohtsuka, Y. Chemistry of diaminomaleonitrile. 1. Selective preparations of monoformyldiaminomaleonitrile and imidazoles by reaction with formicacid. J Org Chem 1976, 41(4): 713-4.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	37430	5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carbonitrile		C₉H₁₂N₄O₄	详情	详情
(X)	33832	[(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate		C₂₆H₂₁BrO₇	详情	详情
(XI)	16903	(Z)-2,3-diamino-2-butenedinitrile;diaminomaleonitrile	1187-42-4	C₄H₄N₄	详情	详情
(XII)	68818	(2R,3R,4S,5R)-2-((benzoyloxy)methyl)-5-(((Z)-1,3-diamino-1-cyanoprop-1-en-2-yl)amino)tetrahydrofuran-3,4-diyl dibenzoate		C₃₀H₂₄N₄O₇	详情	详情
(XIII)	68815	(Z)-4-amino-2,3-bis((trimethylsilyl)amino)but-2-enenitrile		C₁₀H₂₀N₄Si₂	详情	详情
(XIV)	26984	(2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate		C₂₈H₂₄O₉	详情	详情
(XV)	68819	(2R,3R,4S,5R)-2-(5-(aminomethyl)-4-cyano-1H-imidazol-1-yl)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate		C₃₁H₂₂N₄O₇	详情	详情
(XVI)	68821	methyl 4-cyano-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1H-imidazole-5-carbimidate		C₁₁H₁₄N₄O₅	详情	详情
(XVII)	68816	N-formyldiaminomaleonitrile;(Z)-N-(1,3-diamino-1-cyanoprop-1-en-2-yl)formamide		C₅H₄N₄O	详情	详情
(XVIII)	68817	(Z)-N-(3-amino-1-cyano-2-((trimethylsilyl)amino)prop-1-en-1-yl)formamide		C₈H₁₂N₄OSi	详情	详情
(XIX)	68820	(2R,3R,4S,5R)-2-(((Z)-3-amino-1-cyano-2-formamidoprop-1-en-1-yl)amino)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate		C₃₁H₂₄N₄O₈	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

Methylation of D-ribose (XX) with MeOH using HCl yields methyl Dribofuranoside (XXI), which is then benzoylated with BzCl in CHCl3/pyr to give the protected intermediate (XXII). Bromination of methyl ether (XXII) with HBr in AcOH furnishes bromide (X). Acetylation of methyl ether (XXII) with Ac2O and AcOH produces acetate (XIV) .

参考文献中间体

合成目标

【1】 Recondo, E.F., Rinderknecht, H. Eine neue, einfache Synthese des 1-OAcetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranosides. Helv Chim Acta 1959, 42(4): 1171.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	33832	[(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate		C₂₆H₂₁BrO₇	详情	详情
(XIV)	26984	(2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate		C₂₈H₂₄O₉	详情	详情
(XX)	10016	D-Ribose; (3R,4S,5R)-5-(Hydroxymethyl)tetrahydro-2,3,4-furantriol; (2R,3R,4R)-2,3,4,5-Tetrahydroxypentanal	50-69-1	C₅H₁₀O₅	详情	详情
(XXI)	41258	(2R,3S,4R)-2-(hydroxymethyl)-5-methoxytetrahydro-3,4-furandiol		C₆H₁₂O₅	详情	详情
(XXII)	12247	[(2R,3R,4R)-3,4-bis(benzoyloxy)-5-methoxytetrahydro-2-furanyl]methyl benzoate		C₂₇H₂₄O₈	详情	详情

Extended Information