CN101469012B - Method for synthesizing 2-amino-6-methoxy-9-(beta-D-aralino)-9H-purine - Google Patents

Method for synthesizing 2-amino-6-methoxy-9-(beta-D-aralino)-9H-purine Download PDF

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CN101469012B
CN101469012B CN2007101923945A CN200710192394A CN101469012B CN 101469012 B CN101469012 B CN 101469012B CN 2007101923945 A CN2007101923945 A CN 2007101923945A CN 200710192394 A CN200710192394 A CN 200710192394A CN 101469012 B CN101469012 B CN 101469012B
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general formula
reaction
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purine
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CN101469012A (en
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金远锋
陆峰
任建强
李杭
何党军
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HANGZHOU RONGLI MEDICINE SCIENCE & TECHNOLOGY Co Ltd
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention discloses a new synthesis method for 2-amino-6-methoxy-9-(beta-D-arabinose glycosyl)-9H-purine which is a medicine for treating T cell lymphoblast leukemia or lymphoma. The method mainly comprises the following steps: after the acid catalyzed reaction of raw materials, forming a blocking group, carrying out the halogenating reaction in succession, then carrying out the quaternization, and carrying out the de-protecting reaction to generate an end product. The synthesis route has a simple and short route, moderate conditions, easy operation, low cost, high yield and easy amplification, and is suitable for the industrialized production.

Description

The synthetic method of 2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine
Technical field
The problem that the present invention solves provides a kind of T for the treatment of cell lymphoblastic leukemia or the synthetic novel method of lymphoid tumor medicament 2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine.
Technical background
2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine, its general Nelzarabine by name is mainly used in treating T cell lymphoblastic leukemia or lymphoma, and bibliographical information mainly contains following two kinds of synthetic methods at present:
1): the enzyme catalysis synthesis method
It is as shown below that the enzyme catalysis synthesis method is synthesized the route of 2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine:
Figure GSB00000872802300011
The advantage of the method is that step is short, and is three-dimensional single-minded, do not produce steric isomer and isomers, is to synthesize at present 2-amino-6-methoxyl group-9-(β-D-R base)-unique patented method (EP294114A2) of 9H-purine.The shortcoming of the method is: one, used two kinds of enzymes in the building-up process---purine nucleoside phosphorylase and Uridine phosphorylase (H) are all very expensive and be difficult to buy; Its two, the enzymic catalytic reaction time long (J), need about 360 hours; Its three, enzymic catalytic reaction needs a large amount of K 2HPO4 and KH 2PO4 buffered soln (I), thereby need very large reaction unit.
2) chemical synthesis
The chemical synthesis route of the 2-amino of bibliographical information-6-methoxyl group-9-(β-D-R base)-9H-purine is as shown below:
The principal feature of the method is that synthetic route is longer, and yield is lower, and wherein used deprotecting regent boron trichloride (K) is relatively more expensive; and one step of deprotection needs the low temperature (L) of anhydrous and oxygen-free and-78 degree; reaction conditions is very harsh, and complex operation is difficult to amplify and produces.
Summary of the invention
The problem that the present invention solves provides the synthetic novel method of a kind of 2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine (1), and synthetic route is as follows:
Figure GSB00000872802300031
The first step of the present invention is reacted raw materials used D-R (2) and R 1OH reacts under acid catalysis and obtains (3), wherein R 1Represent C1-C6 alkyl, phenyl or by identical or different halogen, trifluoromethyl, trifluoromethoxy optional single replacement or disubstituted C1-C6 alkyl or by identical or different halogen, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl optional single replacement or disubstituted phenyl; R 1OH preferentially selects the C1-C4 alkyl alcohol, and what override was selected is methyl alcohol.The method of this step invention generally is the thermotonus at 0～100 ℃, preferentially be chosen between 30～70 ℃, this step reaction is for improving reaction yield and speeding speed of response and can add strong acid or middle strong acid as catalyzer, most preferred acid is sulfuric acid, in case of necessity adding can absorb the salt of moisture or the carrying out that molecular sieve can promote reaction, anhydrous magnesium sulfate for example, the 4A molecular sieve.The reaction of this step has two products, is substituted radical on the anomeric carbon respectively in α and β position, needn't carry out purifying, is directly used in next step reaction.
Second step reaction of the present invention is the hydroxyl formation blocking group at upper step product, uses R 2X 1Reacting generating compound (4), wherein R 2General formula be:
Figure GSB00000872802300041
R wherein 3Represent the alkyl of hydrogen, C1-C6, the identical or different optional singly replacement or polysubstituted of halogen, trifluoromethyl, trifluoromethoxy, X 1Represent halogen; General R 3Represent the alkyl of hydrogen, C1-C4, the identical or different optional singly replacement or polysubstituted of halogen, trifluoromethyl, trifluoromethoxy, X 1Represent chlorine, bromine, iodine; R commonly used 3Represent hydrogen, identical or different halogen optional single replace or polysubstituted, X 1Represent chlorine, bromine, iodine; Preferred R 3Represent hydrogen, identical or different halogen optional single replace or polysubstituted, X 1Represent chlorine, bromine; Comparatively preferably, R 3Preferential represent that hydrogen, identical or different halogen are optional singly to replace or two replacements X 1Represent chlorine, bromine; R wherein 2More preferential representative is benzyl or 2,4-dichloro benzyl, X 1Representative be chlorine; R wherein 2Most preferred representative is 2,4-dichloro benzyl, X 1Representative be chlorine; Generally reaction between 0-100 ℃ of this reaction, the preferential temperature range of selecting is 20-80 ℃, the solvent that the reaction of this step is selected is the inert organic solvents of commonly using, preferred DMF, THF, DMSO; Add base catalysis during reaction, available alkali comprises sodium hydride, hydrolith, and sodium methylate, sodium ethylate, potassium methylate, potassium ethylate, the alkaline materials such as potassium tert.-butoxide, potassium hydroxide, sodium hydroxide are preferentially selected sodium hydride here.
The present invention's three-step reaction is product of upper step and HX 2Generate compound (5), wherein X 2Represent halogen, general X 2Represent chlorine, bromine, iodine; X 2Preferred chlorine, bromine, the wherein X of representing 2Most preferably represent bromine; General temperature of reaction is at-30～80 ℃, and the preferential reaction temperature is at-10～30 ℃.Reaction solvent is preferentially selected methylene dichloride, ethylene dichloride, chloroform for inert organic solvents commonly used.HX 2Can be directly to add halogen hydride, also can be to add to react to generate HX 2Other raw material, for example acetyl bromide and methyl alcohol, Acetyl Chloride 98Min. and methyl alcohol.
The present invention's four-step reaction is 2-amino-6-X 3Purine (6) generates rear and three-step reaction product (5) reacting generating compound (8) of salt (7) with alkali reaction.X wherein 3Represent halogen, M 1Represent potassium, sodium, calcium, magnesium, lithium; Common X 3Represent chlorine, bromine, iodine, M 1Represent potassium, sodium, calcium; X 3Preferential chlorine, bromine, the M of representing 1Represent potassium, sodium; X wherein 3The best is selected chlorine, M 1Represent sodium; General temperature of reaction is at-30～80 ℃, and preferential selective reaction temperature is-20～30 ℃.Available alkali in the reaction has sodium hydride, lithium hydride, potassium tert.-butoxide, hydrolith, sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, most preferably sodium hydride.Solvent is generally selected tetrahydrofuran (THF), DMF, second eyeball, DMSO, most preferably DMF.Behind the method purifying of reaction product with silica gel column chromatography and crystallization, carry out next step reaction.
The present invention's the 5th step reaction is the 4th step product (8) and CH 3OM 2Reacting generating compound (9), wherein M 2Represent potassium, sodium; M 2Preferentially select sodium.
The present invention's six-step process is that the 5th step product (9) goes protection to obtain compound (1).Going guard method is method well-known to those having ordinary skill in the art, and preferred palladium carbon and ammonium formate are as deprotecting regent.
Perhaps the reaction of the 5th step is that the 4th step product (8) goes protection to obtain compound (10).Going guard method is method well-known to those having ordinary skill in the art, and preferred palladium carbon and ammonium formate are as deprotecting regent.
Six-step process is the 5th step product (10) and CH 3OM 2Reacting generating compound (I), wherein M 2Represent potassium, sodium; M 2Preferentially select sodium;
The synthetic route route that the present invention adopts is simple and direct, mild condition, and easily operation, cost is low, yield is high, be easy to amplify the adaptation suitability for industrialized production.
Below again foregoing of the present invention is described in further detail by the embodiment by some specific examples representatives, but this should be interpreted as that the scope of the above-mentioned theme of the present invention only is confined to following embodiment.All technology of testing based on foregoing of the present invention all belong to scope of the present invention.
Embodiment
Embodiment 1:
The preparation of 1-oxygen-methyl D-pectinose:
Figure GSB00000872802300051
A: with 30g (200mmol) D-R, add the methyl alcohol of 300ml, stir the lower suspension that is, drip the vitriol oil of 5ml, be warmed up to 40 ℃, reacted 2 hours, molten clear, continue reaction after 16 hours, add 6g potassium hydroxide, separate out white precipitate, suction filtration, concentrate to get 32g brown color viscous material, productive rate is 97%.
B:: with 30g (200mmol) D-R, add the methyl alcohol of 300ml, stirring is lower to be suspension, drips the vitriol oil of 5ml, at 0 ℃, reacts after 48 hours, adds 6g potassium hydroxide, separates out white precipitate, and suction filtration concentrates and to get 30g brown color viscous material.
C:: with 30g (200mmol) D-R, add the methyl alcohol of 300ml, stir the lower suspension that is, drip the vitriol oil of 5ml, be warmed up to 68 ℃ of backflows, react after 2 hours, add 6g potassium hydroxide, separate out white precipitate, suction filtration concentrates to get 25g brown color viscous material.
Embodiment 2:
The preparation of 1-oxygen-(2-chloroethyl)-D-R:
Figure GSB00000872802300061
With the D-R of 30g (200mmol), add the ethylene chlorhydrin of 200ml, stir the lower suspension that is, drip the vitriol oil of 5ml, be warmed up to 50 ℃, reacted 2 hours, molten clear, continue reaction after 16 hours, add 6g potassium hydroxide, separate out white precipitate, suction filtration concentrates to get product.
Embodiment 3:
The preparation of 1-oxygen-(2,2-Dichloroethyl)-D-R
Figure GSB00000872802300062
With the D-R of 30g (200mmol), add 2 of 200ml, the 2-dichlroroethanol, stir the lower suspension that is, drip the vitriol oil of 5ml, be warmed up to 50 ℃, reacted 2 hours, molten clear, continue reaction after 16 hours, add the 6g potassium hydroxide PH=7 that neutralizes, separate out white precipitate, suction filtration concentrates to get product.
Embodiment 4:
The preparation of 1-oxygen-phenmethyl-D-R:
Figure GSB00000872802300063
With the D-R of 30g (200mmol), add the phenylcarbinol of 200ml, stir the lower suspension that is, drip the vitriol oil of 5ml, 50 ℃, react after 6 hours, add the 6g potassium hydroxide PH=7 that neutralizes, separate out white precipitate, suction filtration concentrates to get the brown color viscous material.
Embodiment 5:
1-oxygen-methyl-2,3, the preparation of 5-three-oxygen-(2,4-dichloro benzyl)-D-R:
Figure GSB00000872802300071
Product 1-oxygen-methyl D of A: embodiment 1-pectinose 32g (195mmol) adds among the DMF of 350ml, add 28 gram sodium hydrides under the ice-water bath, stir half an hour, drip 2 of 97ml, the 4-dichlorobenzyl chloride is at 35 ℃, reacted 4 hours, to entering in the 2500ml frozen water, there are a large amount of solids to separate out after having reacted, remove top water layer, solid is washed with the dehydrated alcohol bubble, filter, the methylene dichloride dissolving is washed with salt, the organic layer anhydrous magnesium sulfate drying, filtering and concentrating, use ethyl acetate: sherwood oil=recrystallization got white powder solid 77g in 8: 1, and productive rate is 94%.
Product 1-oxygen-methyl D of B: embodiment 1-pectinose 32g (195mmol) adds among the DMF of 350ml, add 28 gram sodium hydrides under the ice-water bath, stir half an hour, drip 2 of 97ml, the 4-dichlorobenzyl chloride at 20 ℃, reacted 16 hours, reacted rear to entering in the 2500ml frozen water, have a large amount of solids to separate out, remove top water layer, solid is washed with the dehydrated alcohol bubble, filter, the methylene dichloride dissolving is with salt washing, organic layer anhydrous magnesium sulfate drying, filter dense doing, use ethyl acetate: sherwood oil=recrystallization got the white powder solid in 8: 1.
Product 1-oxygen-methyl D of C: embodiment 1-pectinose 32g (195mmol) adds among the DMF of 350ml, add 28 gram sodium hydrides under the ice-water bath, stir half an hour, drip 2 of 97ml at 80 ℃, the 4-dichlorobenzyl chloride, reacted 1 hour, and to entering in the 2500ml frozen water, had a large amount of solids to separate out after having reacted, remove top water layer, solid is washed with the dehydrated alcohol bubble, filters the methylene dichloride dissolving, wash with salt, the organic layer anhydrous magnesium sulfate drying filters dense doing, and use ethyl acetate: sherwood oil=recrystallization got the white powder solid in 8: 1.
Embodiment 6:
1-oxygen-methyl-2,3, the preparation of 5-three-oxygen-benzyl-D-R:
Figure GSB00000872802300081
Product 1-oxygen-methyl D of embodiment 1-pectinose 32g (195mmol) adds among the DMF of 350ml, adds 28 gram sodium hydrides under the ice-water bath, stirs half an hour, drip the benzyl chlorine of 65ml, at 35 ℃, reacted 4 hours, to entering in the 2500ml frozen water, there are a large amount of solids to separate out after having reacted, remove top water layer, solid is washed with the dehydrated alcohol bubble, filter, the methylene dichloride dissolving is washed with salt, the organic layer anhydrous magnesium sulfate drying filters the dense product of doing to get.
Embodiment 7:
1-bromo-2,3, the preparation of 5-three-oxygen-(2,4-dichloro benzyl)-D-R:
Figure GSB00000872802300082
The methylene dichloride of A:350ml, the methyl alcohol that adds 11ml, the lower 0 ℃ of acetyl bromide that adds 19.6ml of ice-water bath, stir half an hour, the product 1-oxygen-methyl-2 that adds embodiment 5,3,5-three-oxygen-(2,4-dichloro benzyl)-D-R 77g (183mmol) reacted 6 hours, reacted rear adding 24g sodium bicarbonate neutralization, add the 100ml saturated aqueous common salt, organic layer added anhydrous magnesium sulfate drying one hour after washing with saturated common salt, dense doing to get the brown sticking shape solid of 80g, and adding 250ml anhydrous tetrahydro furan wiring solution-forming is stand-by.
The methylene dichloride of B:350ml, the methyl alcohol that adds 11ml ,-20 ℃ of acetyl bromides that add 19.6ml stir half an hour, add 77g compound (4) (183mmol), reacted 6 hours, and reacted rear adding 24g sodium bicarbonate neutralization, add the 100ml saturated aqueous common salt, after organic layer is washed with saturated common salt, added anhydrous magnesium sulfate drying one hour, dense doing to get brown sticking shape solid, and adding 250ml anhydrous tetrahydro furan wiring solution-forming is stand-by.
The methylene dichloride of C:350ml, the methyl alcohol of adding 11ml, 30 ℃ of acetyl bromides that add 19.6ml, stir half an hour, add 77g compound (4) (183mmol), reacted 6 hours, reacted rear adding 24g sodium bicarbonate neutralization, add the 100ml saturated aqueous common salt, transfer PH=7, organic layer added anhydrous magnesium sulfate drying one hour after washing with saturated common salt, brown sticking shape solid, adding 250ml anhydrous tetrahydro furan wiring solution-forming is stand-by.
Embodiment 8:
1-chloro-2,3, the preparation of 5-three-oxygen-(2,4-dichloro benzyl)-D-R:
Figure GSB00000872802300091
The methylene dichloride of 350ml, the methyl alcohol of adding 11ml, the lower 0 ℃ of Acetyl Chloride 98Min. that adds 19.6ml of ice-water bath, stir half an hour, add product 1-oxygen-methyl-2,3 of embodiment 5,5-three-oxygen-benzyl-D-R 77g (183mmol), reacted 6 hours, and reacted rear adding 24g sodium bicarbonate neutralization, add the 100ml saturated aqueous common salt, after organic layer is washed with saturated common salt, added anhydrous magnesium sulfate drying one hour, dense doing to get product, and adding 250ml anhydrous tetrahydro furan wiring solution-forming is stand-by.
Embodiment 9:
The preparation of 2-amido-6-chloropurine sodium salt:
Figure GSB00000872802300092
A:2-amido-6-chloropurine 30.6g stirs well with the anhydrous tetrahydro furan of 800ml, adds sodium hydride 5.5g under the ice-water bath, react 8 hours stand-by, be the suspension of white.
B:2-amido-6-chloropurine 30.6g stirs well with the dry DMF of 800ml, adds sodium hydride 5.5g under the ice-water bath, reacts 8 hours, gets the solution for later use of brown color.
Embodiment 10:
2-amino-6-chloro-9-[2 ', 3 ', 5 '-three-oxygen-(2,4-dichloro benzyl)-β-D-R base]-preparation of 9H-purine:
Figure GSB00000872802300101
The anhydrous tetrahydrofuran solution of made 2-amido-6-chloropurine sodium salt among A: the embodiment 9 (A), under ice-water bath, drip embodiment 7 made 1-bromo-2,3,5-three-oxygen-(2, the 4-dichloro benzyl)-the D-R tetrahydrofuran solution, react after 20 hours, remove solvent under reduced pressure, add the 400ml ethyl acetate, 500ml water, extraction, the organic layer anhydrous magnesium sulfate drying, remove ethyl acetate under reduced pressure, use ethyl acetate: the white solid 21.5g of sherwood oil=1: 2 recrystallization, yield 23%.
B: among the embodiment 9B made 2-amido-6-chloropurine sodium salt DMF solution, under ice-water bath, drip 8 1-chloro-2 of embodiment, 3,5-three-oxygen-(2, the 4-dichloro benzyl)-anhydrous THF solution of D-R, react after 5 hours, pour in the water, have colloidal solid to separate out, colloidal solid adds the 400ml acetic acid ethyl dissolution, add 500ml water, extraction, the organic layer anhydrous magnesium sulfate drying removes ethyl acetate under reduced pressure, use ethyl acetate: the white solid 17g compound (8) of sherwood oil=1: 2 recrystallization, yield 18%.
Embodiment 11:
2-amino-6-methoxyl group-9-[2 ', 3 ', 5 '-three-oxygen-(2,4-dichloro benzyl)-β-D-R base]-preparation of 9H-purine:
Figure GSB00000872802300102
The product 2-amino of embodiment 10-6-chloro-9-[2 ', 3 ', 5 '-three-oxygen-(2, the 4-dichloro benzyl)-β-D-R base]-9H-purine 21.3g (27.3mmol) adds in the 700ml methyl alcohol, add the 11g sodium methylate, 70 ℃ were refluxed 10 hours, removed solvent under reduced pressure, 800ml ethyl acetate and the extraction of 300ml saturated aqueous common salt.Merge organic layer and add anhydrous magnesium sulfate drying, filter, remove ethyl acetate under reduced pressure, vacuum drying white solid 21g, yield 99%.
Embodiment 12:
The preparation of 2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine:
Figure GSB00000872802300111
The product 2-amino of embodiment 11-6-methoxyl group-9-[2 ', 3 ', 5 '-three-oxygen-(2, the 4-dichloro benzyl)-β-D-R base]-9H-purine 17g (22mmol) adding 600ml methyl alcohol, add 10% palladium carbon 10g, ammonium formiate 28g, 70 ℃ were refluxed 4 hours.With being covered with diatomite filtration, remove catalyzer, be concentrated to 200ml, add the ethyl acetate of 400ml, suction filtration falls white solid (ammonium formiate), then crosses silicagel column and removes remaining ammonium formiate in the solution.Ethyl acetate: methyl alcohol=6: 1 is done irrigation.Remove solvent under reduced pressure, ethyl acetate: methyl alcohol=recrystallization got white solid 5.3g in 6: 1.Yield 81%.
Embodiment 13
The preparation of 2-amino-6-chloro-9-(β-D-R base)-9H-purine:
Figure GSB00000872802300121
The product 2-amino of embodiment 10-6-chloro-9-[2 ', 3 ', 5 '-three-oxygen-(2, the 4-dichloro benzyl)-β-D-R base]-9H-purine 21.3g (27.3mmol) adding 750ml methyl alcohol, add 10% palladium carbon 15g, ammonium formiate 35g, 70 ℃ were refluxed 4 hours.With being covered with diatomite filtration, remove catalyzer, be concentrated into and do adding methyl alcohol 200ml dissolving, add the ethyl acetate of 400ml, suction filtration falls white solid, and filtrate is concentrated to obtain product, and use methyl alcohol: ethyl acetate=recrystallization obtained white solid 5.0g in 1: 6.
Embodiment 14
The preparation of 2-amino-6-methoxyl group-9-(β-D-R base)-9H-purine:
Figure GSB00000872802300122
The product 2-amino of embodiment 13-6-chloro-9-(β-D-R base)-9H-purine 5.0 grams (13.3mmol) add in the 200ml methyl alcohol, the sodium methylate that adds 3g 97%, 70 ℃ were refluxed 10 hours, remove solvent under reduced pressure, be concentrated to 200ml, then the ethyl acetate that adds 400ml is crossed silicagel column and is removed remaining sodium methylate in the solution.Ethyl acetate: methyl alcohol=6: 1 is done irrigation.Remove solvent under reduced pressure, ethyl acetate: the white solid 4.5g of methyl alcohol=6: 1 recrystallization.

Claims (9)

  1. One kind to prepare compound (1) be 2-amino-6-methoxyl group-9-(β-D-R base)-9 HThe method of-purine, its structural formula is as follows:
    It is characterized in that compound (1) obtains by following chemical synthesis route:
    Figure FDA0000274617522
    Wherein:
    R 1Represent methylidene;
    R 2Represent 2,4-dichloro benzyl;
    X 1Represent chlorine;
    X 2Represent bromine;
    X 3Represent chlorine;
    M 1Represent sodium;
    M 2Represent sodium.
  2. 2. by the claims 1 described method, the range of reaction temperature when it is characterized in that general formula compound (2) with alcohol reaction preparation general formula compound (3) is 0 ℃～100 ℃.
  3. 3. by the claims 1 described method, it is characterized in that the range of reaction temperature when general formula compound (3) and halohydrocarbons reaction prepare general formula compound (4) is 0 ℃～100 ℃.
  4. 4. by the claims 1 described method, the range of reaction temperature when it is characterized in that general formula compound (4) with hydrogen halide reaction preparation general formula compound (5) is-30 ℃～80 ℃.
  5. 5. by the claims 1 described method, the range of reaction temperature when it is characterized in that general formula compound (5) with (7) reaction preparation general formula compounds (8) is-30 ℃～80 ℃.
  6. 6. by the claims 2 described methods, the range of reaction temperature when it is characterized in that general formula compound (2) with alcohol reaction preparation general formula compound (3) is 30 ℃～70 ℃.
  7. 7. by the claims 3 described methods, it is characterized in that the range of reaction temperature when general formula compound (3) and halohydrocarbons reaction prepare general formula compound (4) is 20 ℃～80 ℃.
  8. 8. by the claims 4 described methods, the range of reaction temperature when it is characterized in that general formula compound (4) with hydrogen halide reaction preparation general formula compound (5) is-10 ℃～30 ℃.
  9. 9. by the claims 5 described methods, the range of reaction temperature when it is characterized in that general formula compound (5) with (7) reaction preparation general formula compounds (8) is-20 ℃～30 ℃.
CN2007101923945A 2007-12-26 2007-12-26 Method for synthesizing 2-amino-6-methoxy-9-(beta-D-aralino)-9H-purine Active CN101469012B (en)

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Publication number Priority date Publication date Assignee Title
CN1571792A (en) * 2001-03-30 2005-01-26 三角药品公司 Process for the preparation of 2'-halo-beta-l-arabinofuranosyl nucleosides

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Publication number Priority date Publication date Assignee Title
CN1571792A (en) * 2001-03-30 2005-01-26 三角药品公司 Process for the preparation of 2'-halo-beta-l-arabinofuranosyl nucleosides

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Title
ROBERT BARKER等.2,3,5-Tri-O-benzyl-D-nbosyl and -L-arabinosyl Bromides.《J Org Chem》.1961,第26卷(第11期),第4605-4609页.
ROBERT BARKER等.2,3,5-Tri-O-benzyl-D-nbosyl and-L-arabinosyl Bromides.《J Org Chem》.1961,第26卷(第11期),第4605-4609页. *

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