CN102212159B - Preparation method and application of solid-phase organic tin compound - Google Patents

Preparation method and application of solid-phase organic tin compound Download PDF

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CN102212159B
CN102212159B CN2010102080163A CN201010208016A CN102212159B CN 102212159 B CN102212159 B CN 102212159B CN 2010102080163 A CN2010102080163 A CN 2010102080163A CN 201010208016 A CN201010208016 A CN 201010208016A CN 102212159 B CN102212159 B CN 102212159B
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CN102212159A (en
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朱锡桢
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Shenzhen Yinglihua Biological Technology Co ltd
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Abstract

The invention relates to a preparation method and application of a solid-phase organic tin compound. An organic zinc reagent and resin 1 carrying a trialkyl stannic chloride radical are reacted to prepare the solid-phase organic tin compound 2, wherein the equation is the following formula; the resin 1 is the resin or silica gel carrying -SnR2Cl radical; the R radical represents -(CH2)n CH3; n is equal to 0 to 6; the [cat.] represents a catalyst, including Me3SiCl, BrCH2CH2Br, CoBr2 and/or LiCl; the solvent represents a solvent, including tetrahydrofuran (THF), 1,4-dioxane, glycol dimethyl ether, diethyl ether, N,N-dicarbonamide (DMF) and/or N,N-dimethylacetamide; T1 DEG C represents that the reaction temperature is 0 to 80 DEG C; T2 DEG C represents that the reaction temperature is -78 to 100 DEG C; R1 represents an aryl, a heterocycle, a vinyl or an alkyl; and X represents I, Br, Cl or OTf. The invention has the technical effects that: functional groups of many halogenated aromatic compounds with the functional groups are not required to be chemically protected, so the preparation cost is reduced and the preparation difficulty and the like are also reduced.

Description

The preparation method of solid phase organo-tin compound and application thereof
Technical field the present invention relates to the medication preparation applied technical field, particularly relates to the preparation method of solid phase organo-tin compound.
The background technology prior art is in current new drug development, and the solid phase organic reagent is widely used.Its biggest advantage is that purifying is simple, only can remove impurity with filtering, and is subjected to new drug research personnel's welcome deeply.In medicine was synthetic, the Suzuki linked reaction was one of the most frequently used reaction.The preparation of acid reagent has wherein formed a huge industry.But this reaction has its limitation: 1) do not react sometimes; 2) the acid reagent instability that has, production is had any problem.And the Stille linked reaction can overcome above shortcoming, but the toxicity of organotin reagent has restricted the use of Stille linked reaction in medicine is synthetic.For the toxicity that overcomes the liquid organotin reagent and the difficulty on the purifying, Germanization scholar Newmann twentieth century the mid-80 to the solid phase organotin reagent widespread use in organic synthesis done further research work, and successfully to have synthesized be solid phase organo-tin compound (1a) [Gerigk, the U. of skeleton with the polystyrene; Gerlach, M.; Neumann, W.P.; Vieler, R.; Weintritt, V.Synthesis1990,448-452 page or leaf].
Figure GSB00001069066600011
Twentieth century end of the eighties, Canadian Hunter group has proposed to prepare radiopharmaceutic concept with solid phase organotin prerequisite thing, and successively successfully finished the solid phase method preparation [ 131I] IMP[Culbert, P.A.; Hunter, D.H.React.Polym.1993, the 19th volume, 247-253 page or leaf] and [ 131I] MIBG[Hunter, D.H.; Zhu, X.J.Label.Compd.Radiopharm.1999, the 43rd volume, 653-661 page or leaf].2002, Hunter group delivered some valuable solid phase organo-tin compounds and preparation method thereof [Hunter, D.H. again; Janabi, M.WO02/070020A2].Use very active organolithium reagent during Hunter preparation method's defective is to react, caused directly to use many reagent that have functional group's (for example aldehyde radical, fat base, ketone group, cyano group).Thereby many SOLID ORGANIC tin compounds that have functional group are difficult to preparation.
The summary of the invention the technical problem to be solved in the present invention is to avoid above-mentioned the deficiencies in the prior art part and the preparation method that proposes a kind of solid phase organo-tin compound; do not need in the preparation process protective group and deprotection; reduce production stage, increase the charge capacity of solid-phase compound.Utilize the prepared solid phase organo-tin compound of the present invention and the formed radioactive compound of radiohalogen reagent react to can be used for medical diagnosis on disease or the treatment of mammal (comprising the mankind); As mammary cancer, neuroma, brain tumor, Sigma acceptor, MAO acceptor and renal imaging.
The present invention solve the technical problem can be by realizing by the following technical solutions:
Propose a kind of preparation method of solid phase organo-tin compound, utilize the reaction of halogenide and zinc to obtain organic zinc reagent earlier, the resin 1 of recycling organic zinc reagent and load trialkyl tin chloride group, reaction prepares solid phase organo-tin compound 2, and reaction formula is as follows:
Figure GSB00001069066600021
Above-mentioned reaction is to operate under the protection of dry solvent and nitrogen or argon gas;
Resin 1 is load-SnR 2The resin of Cl group or silica gel; R group representative-(CH 2) nCH 3, n=0-6;
[cat.] representative can make R 1The reagent that ZnX forms easily or stablizes and adds comprises Me 3SiCl, BrCH 2CH 2Br, CoBr 2And or LiCl;
The employed solvent of solvent representative reaction comprises THF, 1,4-dioxane, ethylene glycol dimethyl ether, ether, N, N-diformamide (DMF) and or N,N-dimethylacetamide;
T 1℃ representing temperature of reaction is 0 ℃ 80 ℃;
T 2℃ representing temperature of reaction is-78 ℃ 100 ℃;
R 1Represent aromatic base, heterocycle, thiazolinyl or alkyl;
X represents I, Br, Cl, OTf (trifluoromethanesulfonic acid root).
Compare with prior art; technique effect of the present invention is: because the organic zinc preparation reaction temperature that the inventive method is used and, some common functional group reactionses of discord under suitable temperature are as halogen; cyano group; ester group, aldehyde radical, ketone group; nitro etc.; so many halogenated aromatic compounds that have functional group are not needed functional group is carried out chemoproection, so not only reduced preparation cost, and reduced the preparation difficulty and improved production security.In addition, the price of zinc is low, utilizes organic zinc to prepare the solid phase organo-tin compound, can reduce production costs greatly.
Utilize the prepared SOLID ORGANIC tin compound that contains functional group of aforesaid method, perhaps the functional group of prepared SOLID ORGANIC tin compound like this is carried out prepared SOLID ORGANIC tin compound and radiohalogen reagent [X after the chemical conversion *] reaction generation radioactive compound 16 in suitable oxygenant and solvent.Insoluble solid phase byproduct 15 is removed through simple filtration; Contain 16 solution and obtain purifying through simple extraction or by a little anti-phase SPE post or silicagel column.Entire reaction and purifying time can finish in 15 minutes.The radioactivity of the radioactive compound 16 that makes thus can be near used radiohalogen reagent [X *] radioactivity.Reaction formula is as follows:
Figure GSB00001069066600031
Ar represents aromatic nucleus, heterocycle or thiazolinyl;
G represents the substituted radical on the Ar;
[X *] represent the radiohalogen compound, as Na 123I, Na 125I, Na 131I, Na 123I, Na 76Br, 18F 2, 18F-CH 3COOF, 18F-OF 2
Oxidant representative can the iodine oxide negative ion and the oxygenant of bromine negative ion, comprises chloramine-T, acetic acid/hydrogen peroxide mixed solution tertbutyl peroxide, Iodogen, iodine pearl (Iodobead).
Embodiment is described in further detail below in conjunction with the most preferred embodiment shown in the accompanying drawing.
The present invention has utilized the resin of organic zinc reagent and load trialkyl tin chloride group, and as Neumann resin 1a, reaction prepares a series of solid phase organo-tin compound (2) (reaction formula one).Protection and deprotection operation to functional group have successfully been avoided among the Hunter preparation method.Thereby reduced production stage, increased the charge capacity of solid-phase compound.
Reaction formula one is as follows:
Figure GSB00001069066600032
R represents saturated alkyl, comprises methyl, ethyl, normal-butyl;
[cat.] representative can make R 1The reagent that ZnCl forms easily or stablizes and adds comprises Me 3SiCl, BrCH 2CH 2Br, CoBr 2, LiCl;
The employed solvent of solvent representative reaction, comprise tetrahydrofuran THF,, 1,4-dioxane, ethylene glycol dimethyl ether, ether, N, N-diformamide (DMF) and or N,N-dimethylacetamide;
The temperature of T ℃ of representative reaction;
R 1Represent aromatic base, heterocycle, thiazolinyl, alkyl;
X represents I, Br, Cl, OTf.
The preparation of organic zinc reagent utilize bromide or iodide and zinc powder or the reaction of Rieke zinc powder usually and obtain [ a.Knochel, P.*; Leuser, H.; Gong, L.-Z.; Perrone, S.; Kneisel, F.F. " Polyfunctional Zinc Organometalics for Organic Synthesis " in Handbook of Functionalized Organometallics, Knochel, P. (Ed.), Wiley-VCH2005, chapter 7.; b.Oranozinc Reagents (Eds.:Knochel, P.; Jones, P.), Oxford University Press, New York, 1999; c.Krasovskiy, A.; Malakhov, V; Gavryushin, A.; Knochel, P.Angew.Chem.Int.Ed.2006, the 45th volume, 6040-6044 page or leaf].To some inactive halogenide (as muriate) and triflate (Triflates), the preparation of its zincon need add catalyzer and activate zinc, as adding CoBr 2Deng [Kazmierski, I.; Gosmini, C.; Paris, J.-M.; P é richon, J.Synlett, 2006, the 6 volumes, 881.].Some are more sensitive to have the preparation of the zincon of the aromatic compound of reactive hydrogen and heterocycle compound, can insert to make (Mosrin, M. by direct metal; Knochel, P.Org.Lett.2009, the 11st volume, 1837-1840 page or leaf) (reaction formula two).The used reagent of these class methods is R 2NZnClLiCl.Wherein that commonly used is 2,2,6,6-tetramethylpiperidide zinc chloride lithium chloride (TMP-ZnClLiCl).The organic zinc solution that the above method obtains after removing insoluble solid, can be directly and resin 1a reaction form resin 3.
Reaction formula two is as follows:
Figure GSB00001069066600041
In reaction formula three, organic zinc reagent 4-ethoxy carbonyl phenyl zinc iodide and Neumann resin (1a) reaction obtain resin 4.Through alkaline hydrolysis, obtain resin 5 after the acidifying.Resin 5 can be further and amine HNR 1R 2Under the effect of suitable coupling reagent, form corresponding amide resins 11; Perhaps under the effect of suitable coupling reagent, form corresponding carboxylicesters resin 12 with oxy-compound HOR.
Reaction formula three is as follows:
Figure GSB00001069066600051
Solvent represents reaction solvent, comprises THF, 1,4-dioxane, ethylene glycol dimethyl ether, ether, DMF and N,N-dimethylacetamide;
MOH represents the oxyhydroxide of main group element metal, comprises LiOH, NaOH, KOH;
H +Represent protonic acid.
The HOR representative can form the compound of active ester with phenylformic acid, comprises N-maloyl imines (NHS), Pentafluorophenol, polytetrafluoroethylene phenol;
Coupling reagent representative can impel carboxylic acid and amine HNR 1R 2Form the coupling reagent of acid amides, comprise dicyclohexyl carbodiimide/1-hydroxyl-benzo-triazole, DCC-HOBt; Or represent the coupling reagent that can impel carboxylic acid and HOR to form ester group, comprise 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC).
In reaction formula four, 4-cyano-phenyl zinc iodide and Neumann resin (1a) reaction obtain resin 6.Cyano group forms resin 7 through being reduced into aldehyde radical.In liquid phase reaction, become aldehyde radical that many methods are arranged cyano reduction.The present invention has adopted by reported method such as Cha and has utilized three (dihexyl amido) lithium aluminium hydride, and transformation efficiency is almost 100%[Cha, J.S.; Lee, S.E.; Lee, H.S.Organic Preparations and Procedures International1992, the 24th (3) volume, 331].The resin 7 that makes can be proceeded the conversion of functional group and make other solid phase organo-tin compound.For example and R 1NH 2, R 2CO 2H, and R 3The mixture of NC carries out the Ugi reaction and generates the resin 13 that contains two amido linkages; With amine HNR 1R 2Reaction generates resin 17 after reducing; Reaction formula four is as follows:
Figure GSB00001069066600061
Solvent represents reaction solvent, comprises THF, 1,4-dioxane, ethylene glycol dimethyl ether, ether, DMF and N,N-dimethylacetamide;
R represents N, N alkyl amine group, alkyl, alkoxyl group;
HNR 1R 2Represent aliphatic amide or aromatic amine;
[H] representative can be gone back the reagent of the imines of institute's load on the unmodified resin, comprises sodium triacetoxy borohydride, sodium cyanoborohydride;
R 1NH 2Represent aminated compounds;
R 2CO 2H represents carboxylic acid;
R 3NC represents isocyanic ester;
In reaction formula five, 4-iodobenzene methane amide 8 and ZnLiCl reaction form corresponding organic zinc 9.9 and Neumann resin (1a) reaction obtains resin 10.10 through LiAlH 4Be reduced into aldehyde and form resin 7.
Reaction formula five is as follows:
Figure GSB00001069066600071
Following table has been enumerated some SOLID ORGANIC tin compounds that prepared by the above method:
ArI represents iodo aromatic compound and iodo heterogeneous ring compound;
T[℃] centigradetemperature of representative reaction;
The time that t (min) representative reaction is carried out (with a minute note);
The product of products representative reaction.
Embodiment one: the preparation of 4-ethylamino benzonitrile acid esters resin (4)
In the round-bottomed flask of a 25mL, put into 4.0 gram resin 1a (6.8mmol Sn-Cl).Opening clogs with a rubber plug.By the vacuum pump that connects syringe needle the air in the flask is taken out, fed dried nitrogen then.So repeat twice.The tetrahydrofuran (THF) that adds 20 milliliters of dryings then by syringe.Under protection of nitrogen gas, reaction flask is put into ice-water bath.Under magnetic agitation slowly, and injection ethyl4-ethoxycarbonylzinc iodide tetrahydrofuran solution in the reaction flask (0.5M, 16.0mL, 8.0mmol).In ice-water bath, stir after 5 hours, in reaction flask, add the 4mL95% methanol aqueous solution.Stir after 30 minutes under the room temperature, filter to collect resin with the sand core funnel.The resin that obtains is further used distilled water again, and methyl alcohol, acetone and methylene dichloride wash respectively for several times.Obtain a white solid (4.8 gram) after the dry air.
React with trifluoroacetic acid: in the round-bottomed flask of a 15mL, put into 0.30 the gram resin 4,5mL methylene dichloride and 0.5mL trifluoroacetic acid, at room temperature slowly stir 30 minutes after, solid resin is filtered out and washes twice, 3mL methyl alcohol with the 3mL methylene dichloride and wash twice.Obtain the 63.1mg ethyl benzoate after rotary evaporation falls volatile solvent after all filtrate merging, being equivalent to every gram resin 4 loads has 1.40 ± 0.10mmol ethyl benzoate.
Iodine solution reaction: in the round-bottomed flask of a 15mL, put into 0.20 gram resin 4, the second cyanogen solution of 5mL methyl alcohol and 2mL0.2M iodine. after at room temperature slowly stirring 5 hours, in reaction flask, add 0.5mL10%Na 2S 2O 3The aqueous solution is to remove unnecessary iodine. and filter out insoluble solid and use methylene dichloride (2mL) and each wash-out of methyl alcohol (2mL) according to this twice. merging all filtrate afterwards, rotary evaporation falls volatile solvent. and resistates is quenched with ether (15mL) and water (5mL) and is got. and organic layer water (5mL) and saturated brine (5mL) is respectively quenched and is got once.With rotary evaporation behind the anhydrous sodium sulfate drying fall volatile solvent and obtain 69.1mg right-the iodo ethyl benzoate; Be equivalent to every gram resin 4 loads 1.39 ± 0.10mmol ethyl benzoate is arranged.
The preparation of 4 benzoic acid resin (5)
In the round-bottomed flask of a 25mL, put into 1.0 gram resin 4,5mL tetrahydrofuran (THF) and 0.5mL1N lithium hydroxide aqueous solutions.Slowly stirred 5 hours down at 40 ℃.Filter to collect resin with the sand core funnel.The resin that obtains is further used distilled water again, methyl alcohol, and acetone, the mixed solvent of 2N aqueous citric acid solution and methyl alcohol (1: 5), distilled water, methyl alcohol, acetone and washed with dichloromethane are for several times.Obtain a white solid (0.92 gram) after the dry air.
React with trifluoroacetic acid: every gram resin 5 loads have 1.48 ± 0.10mmol phenylformic acid.
Infrared spectra (DRIFT, solid-state): 1695cm -1C=O.
Embodiment two: the preparation of 4-cyano group benzene resin (6)
According to the reaction conditions among the embodiment one, 4-cyano-phenyl zinc iodide and resin 1a are reacted the solid that obtains a white.
The reaction of iodine solution: every gram resin 6 loads have 1.52 ± 0.10mmol 4-cyano group benzene.
Infrared spectra (DRIFT, solid-state): 2240cm -1C ≡ N.
Embodiment three: the preparation of 4-(N-methoxyl group N-methyl-benzamide) resin (10)
The tetrahydrofuran solution (0.5M) of 4-(N-methoxy-N-methylcarbamoyl) phenylzinc Iodide (9) is preparation method (Krasovskiy, the A. according to Knochel; Malakhov, V; Gavryushin, A.; Knochel, P.Angew.Chem.INt.Ed.2006, the 45th volume 6040-6044 page or leaf) be prepared from from 4-iodo-(N-methoxyl group-N-methyl) benzamide (8).
According to the reaction conditions among the embodiment one, 9 and resin 1a of above-mentioned preparation reaction is obtained 4-(N-methoxyl group-N-methyl-benzamide) resin (10).
The reaction of iodine solution: every gram resin 10 loads have 1.39 ± 0.10mmol N-methoxyl group-N-methyl-benzamide.
Embodiment four: preparation (the benzaldehyde)-co-divinylbenzene of 4-phenyl aldehyde resin 7 (Poly-(4-{dibutyl[2-(3-and4-vinylphenyl) ethyl] stannyl).
Method A is according to preparation method (Krasovskiy, the A. of Knochel; Malakhov, V; Gavryushin, A.; Knochel, P.Angew.Chem.Int.Ed.2006, the 45th volume 6040-6044 page or leaf), made the tetrahydrofuran solution (0.5M) of corresponding zn cpds by 4-iodo phenyl aldehyde.
According to the reaction conditions among the embodiment one, it is resin 7 that the tetrahydrofuran solution (0.5M) of the zincon of the 4-benzaldehyde iodine of above-mentioned preparation and resin 1a reaction are obtained a white solid.
The reaction of iodine solution: every gram resin 7 loads have 1.32 ± 0.10mmol phenyl aldehyde.
Infrared spectra (DRIFT, solid-state): 1707cm -1C=O.
Method B puts into 1.0g (1.2mmol) resin 9 and 10mL anhydrous tetrahydro furan in the round-bottomed flask of a 50mL.Under-78 ℃, in bottle, slowly drip 2.5mL1M LiAlH by syringe 4Tetrahydrofuran solution.Continue to stir after 1 hour, in bottle, drip the 1mL cold distilled water with termination reaction.Continue to stir after 15 minutes, filter and collect resin.Use distilled water, methyl alcohol, methylene dichloride, acetone, methyl alcohol are respectively with resin elution for several times.Getting a white solid after the drying is resin 7.
The reaction of iodine solution: every gram resin 7 loads have 1.49 ± 0.10mmol phenyl aldehyde.
Infrared spectra (DRIFT, solid-state): 1707cm -1C=O.
Method C is according to preparation method [Cha, the J.S. of Cha; Lee, S.E.; Lee, H.S.Organic Preparations and Procedures International, 1992, the 24 volumes, 331-334], by 1.5mL1M LiAlH 4Tetrahydrofuran solution and the reaction of dihexyl amine make 1.5mmol three dihexyl amido lithium aluminium hydride (Lithium tris (dihexylamino) aluminum hydride). under stirring at room, above-mentioned solution added in the 25mL round-bottomed flask that fills 1 gram (1.2mmol) resin 6 and 10mL anhydrous tetrahydro furan at leisure.After continuing at room temperature to stir 8 hours, under zero degree, add the 1mL cold distilled water at leisure.Continue to stir after 15 minutes, filter and collect resin.Use distilled water, methyl alcohol, methylene dichloride, acetone, methyl alcohol are respectively with resin elution for several times.Getting a white solid after the drying is resin 7.
The reaction of iodine solution: every gram resin 7 has carried 1.51 ± 0.10mmol phenyl aldehyde.
Infrared spectra (DRIFT, solid-state): 1707cm -1C=O.

Claims (17)

1. the preparation method of a solid phase organo-tin compound, it is characterized in that: utilize the reaction of halogenide and zinc to obtain organic zinc reagent earlier, the resin 1 of recycling organic zinc reagent and load dialkyl group tin chloride group, reaction prepares solid phase organo-tin compound 2, and its reaction formula is as follows:
Figure FSB00001069066500011
Above-mentioned reaction is to operate under the protection of dry solvent and nitrogen or argon gas;
Resin 1 is load-SnR 2The resin of Cl group or silica gel; R group representative-(CH 2) nCH 3, n=0-6;
[cat.] representative can make R 1The reagent that ZnX forms easily or stablizes and adds comprises Me 3SiCl, BrCH 2CH 2Br, CoBr 2And or LiCl;
The employed solvent of solvent representative reaction is tetrahydrofuran (THF), 1,4-dioxane, glycol dimethyl ether, ether, N, dinethylformamide (DMF) and/or N, N-acetic acid dimethylamide;
T 1℃ representing temperature of reaction is 0 ℃-80 ℃;
T 2℃ representing temperature of reaction is-78 ℃-100 ℃;
R 1Represent aromatic base, heterocycle, thiazolinyl or alkyl;
X represents I, Br, Cl or OTf (trifluoromethanesulfonic acid root).
2. the preparation method of solid phase organo-tin compound according to claim 1 is characterized in that: the resin 1 of described load dialkyl group tin chloride group is polyoxyethylene glycol, polystyrene, polyethylene, styrene/ethylene multipolymer, ethylene/propene copolymer, polymeric amide, polypeptide or polyester.
3. the preparation method of solid phase organo-tin compound according to claim 1, it is characterized in that: the resin 1 of described load dialkyl group tin chloride group is 1a or 1b, and the chemical formula of described resin 1,1a and 1b is as follows:
Figure FSB00001069066500021
4. the preparation method of solid phase organo-tin compound according to claim 1 is characterized in that: utilize the aromatic compound and heterocycle compound Ar-H and the R that have reactive hydrogen 2NZnClLiCl reacts to prepare organic zinc reagent, and its reaction formula is as follows;
Figure FSB00001069066500022
Above-mentioned reaction is to operate under the protection of dry solvent and nitrogen or argon gas;
Resin 1 represents load-SnR 2The resin of Cl group or silica gel; R group representative-(CH 2) nCH 3, n=0-6;
The Ar-H representative has aromatic compound and the heterocycle compound of reactive hydrogen;
The employed solvent of solvent representative reaction is tetrahydrofuran (THF), 1,4-dioxane, glycol dimethyl ether, ether, N, dinethylformamide and/or N, N-acetic acid dimethylamide;
T 1The temperature of ℃ representative reaction, 0 ℃-80 ℃;
T 2The temperature of ℃ representative reaction ,-78 ℃-80 ℃;
R ' 2N representative have sterically hindered alkylamino radical, described alkylamino radical comprise 2,2,6,6-tetramethyl-piperidyl (2,2,6,6-tetramethylpiperidide).
5. the preparation method of solid phase organo-tin compound according to claim 4 is characterized in that: the aromatic compound and heterocycle compound (Ar-H) and the R that have reactive hydrogen 2After the NZnClLiCl reaction makes organic zinc reagent, and load-SnR 2The resin of Cl group or silica gel reaction make solid phase organo-tin compound 3 ,-SnR 2R representative-(CH in the Cl group 2) nCH 3, n=0-6, its reaction formula is as follows:
Figure FSB00001069066500031
6. the preparation method of solid phase organo-tin compound according to claim 3 is characterized in that: described organic zinc reagent adopts 4-ethoxy carbonyl phenyl zinc iodide and described resin 1a reaction to obtain resin 4, and its reaction formula is as follows:
Figure FSB00001069066500032
Solvent represents reaction solvent, is tetrahydrofuran (THF), 1,4-dioxane, glycol dimethyl ether, ether, N, dinethylformamide and/or N, N-acetic acid dimethylamide.
7. the preparation method of solid phase organo-tin compound according to claim 3 is characterized in that: described organic zinc reagent adopts 4-cyano-phenyl zinc iodide and described resin 1a reaction to obtain resin 6, and its reaction formula is as follows:
Figure FSB00001069066500033
Solvent represents reaction solvent, is tetrahydrofuran (THF), 1,4-dioxane, glycol dimethyl ether, ether, N, dinethylformamide and/or N, N-acetic acid dimethylamide.
8. the preparation method of solid phase organo-tin compound according to claim 3, it is characterized in that: adopt 4-iodobenzene methane amide 8 and ZnLiCl reaction to form corresponding organic zinc reagent 9, described organic zinc reagent 9 and described resin 1a reaction obtain resin 10, and its reaction formula is as follows:
Figure FSB00001069066500034
9. the application of the prepared solid phase organo-tin compound of preparation method according to claim 6 is characterized in that: the solid phase organo-tin compound resin 4 that makes is carried out alkaline hydrolysis, make resin 5 after the acidifying, its reaction formula is as follows:
Figure FSB00001069066500041
10. the application of the prepared solid phase organo-tin compound of preparation method according to claim 7 is characterized in that: with solid phase organo-tin compound resin 6 and the LiAlHR that makes 3Reaction becomes aldehyde radical with cyano reduction, obtains resin 7, and its reaction formula is as follows:
Figure FSB00001069066500042
R represents N, N-dialkyl amino, alkyl or alkoxyl group.
11. the application of the prepared solid phase organo-tin compound of preparation method according to claim 8 is characterized in that: with solid phase organo-tin compound resin 10 and the LiAlHR that makes 3Reaction is reduced into aldehyde, obtains resin 7, and its reaction formula is as follows:
Figure FSB00001069066500043
R represents hydrogen, alkyl or alkoxyl group.
12. the application according to claim 9 is characterized in that:
The solid phase organo-tin compound resin 5 and the amine reaction that make are generated acid amides, obtain resin 11, its reaction formula is as follows:
Figure FSB00001069066500044
HNR 1R 2Represent aliphatic amide or aromatic amine;
Coupling reagent represents coupling reagent.
13. the application according to claim 9 is characterized in that:
The solid phase organo-tin compound resin 5 and the HOR reaction that make are generated active benzoic ether, obtain resin 12, its reaction formula is as follows:
Figure FSB00001069066500051
The HOR representative can form the compound of active ester with phenylformic acid;
Coupling reagent representative can impel carboxylic acid and HOR to form the reagent of ester group.
14. the application according to claim 13 is characterized in that: solid phase organo-tin compound resin 12 and amine or amino acid reaction generation acid amides with making, obtain resin 11,
Its reaction formula is as follows:
Figure FSB00001069066500052
HNR 1R 2Represent aliphatic amide or aromatic amine.
15. the application according to claim 10 or 11 is characterized in that: the Ugi reaction is taken place solid phase organo-tin compound resin 7 and amine, isocyanic ester and the carboxylic acid that makes, obtain resin 13, its reaction formula is as follows:
Figure FSB00001069066500053
R 1NH 2Represent aminated compounds;
R 2CO 2H represents carboxylic acid;
R 3NC represents isocyanic ester.
16. the application according to claim 15 is characterized in that: with solid phase organo-tin compound resin 13 and the radioactive chemical reagent [X that makes *] reaction makes radioactive compound 16,
Ar represents aromatic nucleus, heterocycle or thiazolinyl;
G represents the substituted radical on the Ar;
[X *] represent the radiohalogen compound;
Oxidant representative can the iodine oxide negative ion and the oxygenant of bromine negative ion.
17. the application according to claim 16 is characterized in that: also comprise the purifying with prepared radioactive compound 16.
CN2010102080163A 2010-06-11 2010-06-11 Preparation method and application of solid-phase organic tin compound Expired - Fee Related CN102212159B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5140070A (en) * 1988-11-07 1992-08-18 Elf Atochem North America, Inc Compositions comprising polymer bond flame retardants
US5220015A (en) * 1988-11-07 1993-06-15 Elf Atochem North America, Inc. Flame retardants compounds
CN101104654A (en) * 2007-07-05 2008-01-16 复旦大学 Polymer containing multiple functional groups at end of the same and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5140070A (en) * 1988-11-07 1992-08-18 Elf Atochem North America, Inc Compositions comprising polymer bond flame retardants
US5220015A (en) * 1988-11-07 1993-06-15 Elf Atochem North America, Inc. Flame retardants compounds
CN101104654A (en) * 2007-07-05 2008-01-16 复旦大学 Polymer containing multiple functional groups at end of the same and preparation method thereof

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