(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol -Drug Synthesis Database

【结构式】

【分子编号】29141

【品名】(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol

【CA登记号】582-52-5

【分子式】C₁₂H₂₀O₆

【分子量】260.2872

【元素组成】C 55.37% H 7.74% O 36.88%

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：(I)

The reaction of 1,2:5.6-di-O-isopropyliden-D-glucofuranose (I) with 3-chloro-N,N-dimethylaminopropane (II) by means of NaOH in refluxing dioxane gives 1,2:5,6-di-O-isopropylidene-3-O-[3'-(N,N-dimethylamino)propyl]-D-gluco-furanose (III), which is partially hydrolyzed with HCl in water.

参考文献中间体

合成目标

【1】 Gordon, P. (Boston Life Sciences, Inc.); Method of enhancing learning and/or memory in warm blooded animals. US 3965262 .
【2】 Hopkins, S.J.; Serradell, M.N.; Castaner, J.; Therafectin. Drugs Fut 1985, 10, 4, 301.

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)	29141	(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	582-52-5	C₁₂H₂₀O₆	详情	详情
(II)	24581	3-(Dimethylamino)propyl chloride; 3-Chloro-N,N-dimethyl-1-propanamine	5407-04-5	C₅H₁₂ClN	详情	详情
(III)	29142	3-([(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl]oxy)-N,N-dimethyl-1-propanamine		C₁₇H₃₁NO₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (I) with methanesulfonyl chloride and pyridine gives the mesylate (II), which by treatment with sodium azide in DMF is converted into 3-azido-3-deoxy-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (III). Selective hydrolysis of (III) with 1N HCl in ethanol affords 3-azido-3-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose (IV) (1), which is oxidized with sodium metaperiodate to the aldehyde (V). The reduction of (V) with NaBH4 in EtOH gives 3-azido-3-deoxy-1,2-O-isopropylidene-alpha-D-xylofuranose (VI), which is treated with tosyl chloride and pyridine to yield the corresponding 5-O-tosylate (VII) (2). The reaction of (VII) with potassium thiobenzoate (VIII) in hot DMF gives 3-azido-5-S-benzoyl-3-deoxy-1,2-O-isopropylidene-5-thio-alpha-D-xylofuranose (IX), which is treated successively with NaOMe in methanol, to induce cyclization, with refluxing HCl in methanol, to eliminate the isopropylidene group, and finally with acetic anhydride to furnish 1,2,4-tri-O-acetyl-3-azido-3-deoxy-5-thio-D-xylopyranose (X). The condensation of (X) with 4-nitrothiophenol (XI) by means of trimethylsilyl triflate in dichloromethane yields the corresponding acylated dithiopyranoside, which is finally deacetylated with sodium methoxide in methanol.

参考文献中间体

合成目标

【1】 Meyer, W.; Synthese der 3-Amino-3-desoxy- und 3,6-Diamino-3,6-didesoxy-D-glucose. Chem Ber 1968, 101, 11, 3802-07.
【2】 Kuzuhara, H.; Ohrui, H.; Emoto, S.; Conversion of D-Glucose into d-Oxybiotin. Part I. Synthesis of 2,5-anhydro-3-azido-3-deoxy-D-xylose dimethyl acetal. Agr Biol Chem 1970, 34, 3, 375-380.
【3】 Kovácsné Bozó, E.; Kuszmann, J.; Szabó, G.; Boros, S.; Moravcsik, I. (Gedeon Richter Ltd.); Novel anticoagulant glycosides and pharmaceutical compsns. thereof. EP 0907656; WO 9749716 .

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)	29141	(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	582-52-5	C₁₂H₂₀O₆	详情	详情
(II)	38930	(3aR,5R,6R,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-6-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]tetrahydrofuro[2,3-d][1,3]dioxole		C₁₅H₂₆O₆S	详情	详情
(III)	38931	(3aR,5S,6S,6aR)-6-azido-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; (3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl azide		C₁₂H₁₉N₃O₅	详情	详情
(IV)	38932	(1R)-1-[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-1,2-ethanediol		C₉H₁₅N₃O₅	详情	详情
(V)	38933	(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde		C₈H₁₁N₃O₄	详情	详情
(VI)	38934	[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methanol		C₈H₁₃N₃O₄	详情	详情
(VII)	38935	[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl 4-methylbenzenesulfonate		C₁₅H₁₉N₃O₆S	详情	详情
(VIII)	38936	potassium benzenecarbothioate		C₇H₅KOS	详情	详情
(IX)	38937	S-[[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl] benzenecarbothioate		C₁₅H₁₇N₃O₄S	详情	详情
(X)	38938	(2R,3R,4S,5S)-2,5-bis(acetoxy)-4-azidotetrahydro-2H-thiopyran-3-yl acetate		C₁₁H₁₅N₃O₆S	详情	详情
(XI)	38898	4-nitrophenylhydrosulfide; 4-nitrobenzenethiol	1849-36-1	C₆H₅NO₂S	详情	详情
(XII)	38939	(2S,3R,4S,5S)-5-(acetoxy)-4-azido-2-[(4-nitrophenyl)sulfanyl]tetrahydro-2H-thiopyran-3-yl acetate		C₁₅H₁₆N₄O₆S₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Treatment of 1,2,5,6-diisopropylidene-D-glucofuranose (I) with trifluoromethanesulfonic anhydride and pyridine provides triflate (II), which is then displaced with sodium azide to furnish the 3-azido derivative (III). Oxidative cleavage of the 5,6-diol acetonide of (III) by means of periodic acid leads to aldehyde (IV). Further oxidation of (IV) with a catalytic amount of ruthenium trichloride in the presence of sodium periodate affords carboxylic acid (V). After activation of acid (V) with oxalyl chloride, coupling with methylamine provides amide (VI). Acidic hydrolysis of the remaining 1,2-acetonide of (VI) in the presence of acetic anhydride gives rise to diacetate (VII). Silylation of 6-chloropurine (VIII), followed by coupling with the diacetyl ribofuranuronic acid derivative (VII) in the presence of trimethylsilyl triflate yields the purine glycoside (IX). The acetate ester group of (IX) is then removed by methanolysis in the presence of either methylamine or triethylamine, to produce alcohol (X). Subsequent azido group reduction in (X) by means of triphenylphosphine leads to amine (XI), which is then protected as the N-Boc derivative (XII) employing di-t-butyl dicarbonate.

参考文献中间体

合成目标

【1】 Masamune, H.; Scott, R.W.; Deninno, M.P. (Pfizer Products Inc.); Cpds. for the treatment of ischemia. EP 1216257; JP 2003510331; WO 0123399 .

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)	29141	(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	582-52-5	C₁₂H₂₀O₆	详情	详情
(II)	61299	(3aR,5R,6S,6aR)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl trifluoromethanesulfonate		C₁₃H₁₉F₃O₈S	详情	详情
(III)	61300	(3aR,5S,6R,6aR)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl azide; (3aR,5S,6R,6aR)-6-azido-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole		C₁₂H₁₉N₃O₅	详情	详情
(IV)	61363	(3aR,5S,6R,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde		C₈H₁₁N₃O₄	详情	详情
(V)	31364	(5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal		C₂₈H₃₅NO₃	详情	详情
(VI)	31365	tert-butyl[[(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl (2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl ether		C₃₀H₅₆O₃Si	详情	详情
(VII)	31366	2-[(2E,6Z,10E)-7-(hydroxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]-1H-isoindole-1,3(2H)-dione		C₂₈H₃₇NO₃	详情	详情
(VIII)	17692	6-Chloropurine; 6-chloro-9H-purine	87-42-3	C₅H₃ClN₄	详情	详情
(IX)	61367	(2R,3R,4R,5S)-4-azido-2-(6-chloro-9H-purin-9-yl)-5-[(methylamino)carbonyl]tetrahydro-3-furanyl acetate		C₁₃H₁₃ClN₈O₄	详情	详情
(X)	61368	(2S,3S,4R,5R)-3-azido-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-N-methyltetrahydro-2-furancarboxamide		C₁₁H₁₁ClN₈O₃	详情	详情
(XI)	61369	(2S,3S,4R,5R)-3-amino-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-N-methyltetrahydro-2-furancarboxamide		C₁₁H₁₃ClN₆O₃	详情	详情
(XII)	61370	tert-butyl (2S,3S,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-2-[(methylamino)carbonyl]tetrahydro-3-furanylcarbamate		C₁₆H₂₁ClN₆O₅	详情	详情

Extended Information