(nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone -Drug Synthesis Database

【结构式】

【分子编号】37778

【品名】(nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone

【CA登记号】21272-85-5

【分子式】C₇H₇NO₄S

【分子量】201.20292

【元素组成】C 41.79% H 3.51% N 6.96% O 31.81% S 15.94%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

A new enantioselective synthesis of neplanocin A has been reported: The enantiocontrolled condensation of the 6-chloropurine (I) with cis-1,3-bis(benzoyloxy)-4-cyclopentene (II) catalyzed by a chiral Pd catalyst gives the alkylated purine (III), which is condensed with the nitrosulfone (IV) by means of PPh3 and TEA yielding the intermediate (V). Epoxidation of (V) with MCPBA in dichloromethane affords the epoxide (VI), which is oxidized with O3 and DBU in methanol/THF giving the cyclopentenecarboxylate (VII). The esterification of the beta-OH group of (VII) with 4-nitrobenzoic acid (VIII), PPh3 and DEAD in THF, using a Mitsunobu reaction to invert the OH group, yields the ester (IX), with the desired alpha-OH configuration. The reduction of (IX) with DIBAL in THF/dichloromethane affords the unsaturated the diol (X), which is dihydroxylated with OsO4 and NMO in acetone/water providing the tetraol (XI). The reaction of (XI) with 2,2-dimethoxypropane and TsOH gives the diacetonide (XII), which is selectively monodeprotected with FeCl3 on silica gel yielding the dihydroxylated acetonide (XIII). The regioselective hydroxylation of the primary OH of (XIII) with pivaloyl chloride (Piv-Cl) in pyridine yields the pivalate (XIV), which is dehydrated with SOCl2 in DMF/pyridine affording the fully protected 6-chloropurine derivative (XV). Compound (XV) is treated with ammonia in order to eliminate the pivaloyl group and to form the adenine derivative (XVI), which is finally treated with hot aqueous HCl to eliminate the acetonide group.

参考文献中间体

合成目标

【1】 Madsen, R.; Brown, B.; Guile, S.D.; Trost, B.M.; Palladium-catalyzed enantioselective synthesis of carbanucleosides. J Am Chem Soc 2000, 122, 25, 5947.

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)	17692	6-Chloropurine; 6-chloro-9H-purine	87-42-3	C₅H₃ClN₄	详情	详情
(II)	37776	(1R,4S)-4-(benzoyloxy)-2-cyclopenten-1-yl benzoate		C₁₉H₁₆O₄	详情	详情
(III)	41036	(1S,4R)-4-(6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl benzoate		C₁₇H₁₃ClN₄O₂	详情	详情
(IV)	37778	(nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone	21272-85-5	C₇H₇NO₄S	详情	详情
(V)	41037	6-chloro-9-[(1R,4S)-4-[(S)-nitro(phenylsulfonyl)methyl]-2-cyclopenten-1-yl]-9H-purine; (S)-[(1S,4R)-4-(6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl](nitro)methyl phenyl sulfone		C₁₇H₁₄ClN₅O₄S	详情	详情
(VI)	41038	(S)-[(1S,2S,4R,5R)-4-(6-chloro-9H-purin-9-yl)-6-oxabicyclo[3.1.0]hex-2-yl](nitro)methyl phenyl sulfone; 6-chloro-9-[(1R,2R,4S,5S)-4-[(S)-nitro(phenylsulfonyl)methyl]-6-oxabicyclo[3.1.0]hex-2-yl]-9H-purine		C₁₇H₁₄ClN₅O₅S	详情	详情
(VII)	41039	methyl (3S,4R)-4-(6-chloro-9H-purin-9-yl)-3-hydroxy-1-cyclopentene-1-carboxylate		C₁₂H₁₁ClN₄O₃	详情	详情
(VIII)	18119	4-nitrobenzoic acid; p-nitrobenzoic acid	62-23-7	C₇H₅NO₄	详情	详情
(IX)	41040	(1R,5R)-5-(6-chloro-9H-purin-9-yl)-3-(methoxycarbonyl)-2-cyclopenten-1-yl 4-nitrobenzoate		C₁₉H₁₄ClN₅O₆	详情	详情
(X)	41041	(1R,5R)-5-(6-chloro-9H-purin-9-yl)-3-(hydroxymethyl)-2-cyclopenten-1-ol		C₁₁H₁₁ClN₄O₂	详情	详情
(XI)	41042	(1S,2S,3S,4R)-4-(6-chloro-9H-purin-9-yl)-1-(hydroxymethyl)-1,2,3-cyclopentanetriol		C₁₁H₁₃ClN₄O₄	详情	详情
(XII)	41043			C₁₇H₂₁ClN₄O₄	详情	详情
(XIII)	41044	(3aS,4S,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-4-(hydroxymethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol		C₁₄H₁₇ClN₄O₄	详情	详情
(XIV)	41045	[(3aS,4S,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-4-hydroxy-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl pivalate		C₁₉H₂₅ClN₄O₅	详情	详情
(XV)	41046	[(3aR,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl pivalate		C₁₉H₂₃ClN₄O₄	详情	详情
(XVI)	41047	[(3aR,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol		C₁₄H₁₇N₅O₃	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 enantiocontrolled condensation of the protected guanine (I) with cis-1,3-bis(benzoyloxy)-4-cyclopentene (II) catalyzed by a chiral Pd catalyst gives the alkylated guanine (III), which is condensed with the nitrosulfone (IV) by means of PPh3 and TEA to yield the intermediate (V). The oxidation of (V) with oxone, tetramethylguanidine, and Na2CO3 in methanol/dichloromethane affords the cyclopentenecarboxylate (VI), which is finally reduced with calcium borohydride and deprotected with ammonia to provide the target compound.

参考文献中间体

合成目标

【1】 Madsen, R.; Brown, B.; Guile, S.D.; Trost, B.M.; Palladium-catalyzed enantioselective synthesis of carbanucleosides. J Am Chem Soc 2000, 122, 25, 5947.

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)	37775	2-(acetamido)-9H-purin-6-yl diphenylcarbamate		C₂₀H₁₆N₆O₃	详情	详情
(II)	37776	(1R,4S)-4-(benzoyloxy)-2-cyclopenten-1-yl benzoate		C₁₉H₁₆O₄	详情	详情
(III)	37777	(1S,4R)-4-(2-(acetamido)-6-[[(diphenylamino)carbonyl]oxy]-9H-purin-9-yl)-2-cyclopenten-1-yl benzoate		C₃₂H₂₆N₆O₅	详情	详情
(IV)	37778	(nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone	21272-85-5	C₇H₇NO₄S	详情	详情
(V)	37779	2-(acetamido)-9-[(1R,4S)-4-[(S)-nitro(phenylsulfonyl)methyl]-2-cyclopenten-1-yl]-9H-purin-6-yl diphenylcarbamate		C₃₂H₂₇N₇O₇S	详情	详情
(VI)	37780	methyl (1S,4R)-4-(2-(acetamido)-6-[[(diphenylamino)carbonyl]oxy]-9H-purin-9-yl)-2-cyclopentene-1-carboxylate		C₂₇H₂₄N₆O₅	详情	详情

Extended Information