CN104788482B - A kind of method preparing 2-aminopyrimidine-5-boric acid pinacol ester - Google Patents
A kind of method preparing 2-aminopyrimidine-5-boric acid pinacol ester Download PDFInfo
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- CN104788482B CN104788482B CN201510032746.5A CN201510032746A CN104788482B CN 104788482 B CN104788482 B CN 104788482B CN 201510032746 A CN201510032746 A CN 201510032746A CN 104788482 B CN104788482 B CN 104788482B
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- boric acid
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- 238000000034 method Methods 0.000 title claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 10
- -1 chlorine 5 Bromopyrimidines Chemical class 0.000 claims abstract description 9
- ZZPNDIHOQDQVNU-UHFFFAOYSA-N 2-hydroxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(O)OC1(C)C ZZPNDIHOQDQVNU-UHFFFAOYSA-N 0.000 claims abstract description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract description 7
- WHQHIIFNBWIJSG-UHFFFAOYSA-N C(C)(C)OOB(O)O.OC(C)(C)C(C)(C)O Chemical compound C(C)(C)OOB(O)O.OC(C)(C)C(C)(C)O WHQHIIFNBWIJSG-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 5
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 8
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims description 8
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000004090 dissolution Methods 0.000 claims description 5
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 239000004327 boric acid Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000004210 ether based solvent Substances 0.000 claims description 2
- UQXKXGWGFRWILX-UHFFFAOYSA-N ethylene glycol dinitrate Chemical compound O=N(=O)OCCON(=O)=O UQXKXGWGFRWILX-UHFFFAOYSA-N 0.000 claims description 2
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 239000007795 chemical reaction product Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000001953 recrystallisation Methods 0.000 abstract description 2
- DAJLHNABGVYSOO-UHFFFAOYSA-N boric acid;2,3-dimethylbutane-2,3-diol Chemical class OB(O)O.CC(C)(O)C(C)(C)O DAJLHNABGVYSOO-UHFFFAOYSA-N 0.000 abstract 3
- 125000001246 bromo group Chemical group Br* 0.000 abstract 1
- 238000007789 sealing Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000001914 filtration Methods 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- YOVVNQKCSKSHKT-HNNXBMFYSA-N (2s)-1-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-hydroxypropan-1-one Chemical compound C1CN(C(=O)[C@@H](O)C)CCN1CC1=C(C)C2=NC(C=3C=NC(N)=NC=3)=NC(N3CCOCC3)=C2S1 YOVVNQKCSKSHKT-HNNXBMFYSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- UHRHPPKWXSNZLR-UHFFFAOYSA-N 5-bromopyrimidin-2-amine Chemical compound NC1=NC=C(Br)C=N1 UHRHPPKWXSNZLR-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229950004111 apitolisib Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- XMGMFRIEKMMMSU-UHFFFAOYSA-N phenylmethylbenzene Chemical group C=1C=CC=CC=1[C]C1=CC=CC=C1 XMGMFRIEKMMMSU-UHFFFAOYSA-N 0.000 description 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229940069559 votrient Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of method preparing 2 aminopyrimidine 5 boric acid pinacol esters, from raw material 2 chloropyrimide, at BF3‑Et2Under O catalysis, bromo is occurred to obtain 2 chlorine 5 Bromopyrimidines with NBS；This intermediate and n Bu subsequently3MgLi 20～10 DEG C of reactions, be subsequently added methoxyl group boric acid pinacol ester or isopropoxy boric acid pinacol ester carry out boronation after obtain 2 chloropyrimide 5 boric acid pinacol esters；It is subsequently added in ammonia or methanolic ammonia solution, after 80～100 DEG C of sealing reactions, obtains 2 aminopyrimidine 5 boric acid pinacol esters.Synthetic technological condition of the present invention is gentle, it is to avoid ultralow temperature reaction, and reacts and can be carried out continuously, and only need to carry out simple recrystallization when end product can get sterling.
Description
Technical field
The present invention relates to a kind of method preparing 2-aminopyrimidine-5-boric acid pinacol ester, belong to pharmaceutical intermediate synthesis field.
Technical background
Known listing or in grinding new drug I type PI3K inhibitor Apitolisib and inhibitors of kinases Votrient, all contain 2-aminopyrimidine group, and have more research will this segment as important construction unit.2-aminopyrimidine-5-boric acid pinacol ester, as one of them key intermediate, is disclosed the synthetic method of data: mainly include 1 at present) use 2-amino-5-iodine pyrimidine and pinacol borine at Pd (PPh)4Under catalysis, (reference: Org.Biomol.Chem., 2011,9,3139) or 2-amino-5-Bromopyrimidine and connection boric acid pinacol ester are at PdCl2Coupling in the presence of dppf (reference: WO 2012/109423 A1)；2) after using same raw material amino Boc (reference: CN102399235A and CN102367260A) or diphenyl methylene (reference: US 2008/0269523 A1) to be protected; (or do not protect directly; reference: Eur.J.Org.Chem.2007; 5712) ultralow temperature reaction at butyl lithium/triisopropyl borate ester/-78 DEG C is used to be initially formed boric acid; subsequently after deprotection, react into ester followed by with pinacol.
Said method: 1) coupling catalyst large usage quantity, cost is high, and product has heavy-metal residual；2) when amino uses benzophenone protection, can not get condensation product according to the patented method first step, need all to protect with by nitrogen when using Boc protection；Amino does not protect the method yield instability of direct reaction, poor reproducibility, and such method all to there is the shortcoming needing ultralow temperature to react.
Summary of the invention
The technical problem to be solved is to provide a kind of new method preparing 2-aminopyrimidine-5-boric acid pinacol ester, comprises the following steps:
The first step, at BF3-Et2Under O catalytic action, 2-chloropyrimide and NBS back flow reaction in acetonitrile or glycol dinitrate ether solvents, obtain 2-chloro-5-Bromopyrimidine；
Second step, maintain the temperature at-20～-10 DEG C 2.5M n-BuLi is joined in n-BuMgBr, be prepared as n-Bu3MgLi, the 2-chloro-5-Bromopyrimidine maintaining this temperature the first step to be obtained subsequently is dissolved in oxolane and instills in above-mentioned solution, it is incubated 1 hour, dropping methoxyl group boric acid pinacol ester or isopropoxy boric acid pinacol ester, be incubated 1 hour, and solution is raised to room temperature, it is stirred overnight, add saturated ammonium chloride cancellation, be extracted with ethyl acetate, be evaporated and obtain 2-chloropyrimide-5-boric acid pinacol ester；
3rd step, in autoclave pressure, 2-chloropyrimide-5-boric acid pinacol the ester obtained by second step adds in ammonia or ammonia methanol, 80～100 DEG C are reacted 6 hours, solution filters after adding oxolane or acetic acid ethyl dissolution after being spin-dried for, and again adds recrystallizing methanol after solvent evaporated and obtains 2-aminopyrimidine-5-boric acid pinacol ester.
Further, in the described first step, 2-chloropyrimide and NBS, BF3-Et2The mol ratio of O is 1: 1-1.5: 0.05-0.3.
Further, in described second step, the mol ratio of n-BuLi Yu n-BuMgBr is 2: 1；2-chloro-5-Bromopyrimidine and n-Bu3The mol ratio of MgLi, methoxyl group boric acid pinacol ester or isopropoxy boric acid pinacol ester is 1: 0.4-0.5: 1.1-1.5.
Further, in described 3rd step, 2-chloropyrimide-5-boric acid pinacol ester and ammonia or ammonia Methanol Molar amount ratio 1: 2-5.
Reaction equation is as follows:
Invention beneficial effect
Synthetic technological condition of the present invention is gentle, it is to avoid ultralow temperature reaction, and reacts and can be carried out continuously, and only need to carry out simple recrystallization when end product can get sterling.
Detailed description of the invention
Embodiment 1
A kind of method preparing 2-aminopyrimidine-5-boric acid pinacol ester, comprises the following steps:
In reaction bulb, add 2-chloropyrimide 11.5g (0.1mol), bromide reagent NBS 21.3g (0.12mol) and acetonitrile 80mL, under room temperature, add catalytic amount BF3-Et2O 2.8g (0.02mol), after addition, is warming up to back flow reaction 5-8 hour, and TLC detects after completion of the reaction, cooling, after filtering out insoluble solids, after decompression solvent distillation, adds acetic acid ethyl dissolution, then is added dropwise to the saturated Na of 45mL2CO3Solution washs, and separates organic layer, and water layer adds 60mL ethyl acetate, then after secondary clearing, after merging organic layer, saturated aqueous common salt washs, and is spin-dried for obtaining light yellow 2-chloro-5-Bromopyrimidine solid 14.1g, is directly used in the next step.1H-NMR (400MHz, CDCl3): 8.70 (s, 2H).
nullUnder nitrogen protection，The n-BuMgBr solution (1M tetrahydrofuran solution) that addition 29.2mL prepares in advance in reaction bulb is cooled to-20 DEG C，In maintaining subsequently, temperature drips 23.4mL n-BuLi (2.5M hexane solution)-20～-10 DEG C，Drip complete insulated and stirred after 30 minutes，The 2-chloro-5-Bromopyrimidine 14.1g (73mmol) that the first step is obtained and anhydrous tetrahydro furan 40mL，Drip Bi Baowen 1 hour，TLC detection exchange is completely，Maintain the anhydrous tetrahydrofuran solution of this temperature dropping methoxyl group boric acid pinacol ester 13.3g (84mmol) subsequently，It is incubated 1 hour，Solution is warmed to room temperature naturally，It is stirred overnight，Adding saturated ammonium chloride cancellation adjusts PH to be 4-5，Ethyl acetate 70mL extracts，Merging organic layer is evaporated and obtains 2-chloropyrimide-5-boric acid pinacol ester solid crude product 12.1g，G/C content is more than 95%，Yield 69%，Can be directly entered in next step reaction；1H-NMR (400MHz, CDCl3): 8.60 (s, 2H), 1.29 (s, 12H).
In 100mL autoclave pressure, 2-chloropyrimide-5-boric acid pinacol ester 12.1g (50mmol) obtained by second step adds in 22.5g 28% ammonia (180mmol), 100 DEG C seal reaction 6 hours, solution filters after adding 150mL acetic acid ethyl dissolution after being spin-dried for, again add recrystallizing methanol after solvent evaporated and obtain white crystalline solid 2-aminopyrimidine-5-boric acid pinacol ester 8.6g, yield 78%.1H-NMR (400MHz, CDCl3): 8.58 (s, 2H), 5.80 (s, 2H), 1.32 (s, 12H)；
Embodiment 2
A kind of method preparing 2-aminopyrimidine-5-boric acid pinacol ester, comprises the following steps:
In reaction bulb, add 2-chloropyrimide 11.5g (0.1mol), bromide reagent NBS 21.3g (0.12mol) and glycol dimethyl ether 80mL, under room temperature, add catalytic amount BF3-Et2O 4.2g (0.03mol), after addition, is warming up to back flow reaction 5-8 hour, and TLC detects after completion of the reaction, cooling, after filtering out insoluble solids, after decompression solvent distillation, adds acetic acid ethyl dissolution, then is added dropwise to the saturated Na of 45mL2CO3Solution washs, and separates organic layer, and water layer adds 60mL ethyl acetate, then after secondary clearing, after merging organic layer, saturated aqueous common salt washs, and is spin-dried for obtaining light yellow 2-chloro-5-Bromopyrimidine solid 13.2g, is directly used in the next step.1H-NMR (400MHz, CDCl3): 8.70 (s, 2H).
nullUnder nitrogen protection，Under nitrogen protection，The n-BuMgBr solution (1M tetrahydrofuran solution) that addition 29.2mL prepares in advance in reaction bulb is cooled to-20 DEG C，In maintaining subsequently, temperature drips 23.4mL n-BuLi (2.5M hexane solution)-20～-10 DEG C，Drip complete insulated and stirred after 30 minutes，The 2-chloro-5-Bromopyrimidine 14.1g (73mmol) that the first step is obtained and anhydrous tetrahydro furan 40mL，Drip Bi Baowen 1 hour，TLC detection exchange is completely，Maintain the anhydrous tetrahydrofuran solution of this temperature dropping isopropoxy boric acid pinacol ester 15.6g (84mmol) subsequently，It is incubated 1 hour，Solution is warmed to room temperature naturally，It is stirred overnight，Adding saturated ammonium chloride cancellation adjusts PH to be 4-5，Ethyl acetate 80mL extracts，Merging organic layer is evaporated and obtains 2-chloropyrimide-5-boric acid pinacol ester solid crude product 10.5g，G/C content is more than 96%，Yield 64%，Can be directly entered in next step reaction；1H-NMR (400MHz, CDCl3): 8.60 (s, 2H), 1.29 (s, 12H).
In 100mL autoclave pressure, 2-chloropyrimide-5-boric acid pinacol ester 7.2g (30mmol) obtained by second step adds in 9.42mL 7M methanolic ammonia solution (66mmol), 80 DEG C seal reaction 8 hours, solution adds filtration after 100mL oxolane dissolves after being spin-dried for, again add recrystallizing methanol after solvent evaporated and obtain white crystalline solid 2-aminopyrimidine-5-boric acid pinacol ester 4.4g, yield 66%.1H-NMR (400MHz, CDCl3): 8.58 (s, 2H), 5.80 (s, 2H), 1.32 (s, 12H).
Claims (2)
1. the method preparing 2-aminopyrimidine-5-boric acid pinacol ester, it is characterised in that comprise the following steps:
The first step, at 0.05-0.3 equivalent BF3-Et2Under O catalytic action, 2-chloropyrimide and 1-1.5 equivalent NBS back flow reaction in acetonitrile or glycol dinitrate ether solvents, obtain 2-chloro-5-Bromopyrimidine；
Second step, maintains the temperature at-20 ~-10 DEG C and joins in n-BuMgBr by 2.5M n-BuLi, be prepared as n-Bu3MgLi, the 2-chloro-5-Bromopyrimidine maintaining this temperature the first step to be obtained subsequently is dissolved in oxolane and instills in above-mentioned solution, it is incubated 1 hour, dropping methoxyl group boric acid pinacol ester or isopropoxy boric acid pinacol ester, be incubated 1 hour, and solution is raised to room temperature, it is stirred overnight, add saturated ammonium chloride cancellation, be extracted with ethyl acetate, be evaporated and obtain 2-chloropyrimide-5-boric acid pinacol ester；
3rd step, in autoclave pressure, 2-chloropyrimide-5-boric acid pinacol the ester obtained by second step adds in 2-5 equivalent ammonia or in methanolic ammonia solution, 80 ~ 100 DEG C are reacted 6 hours, solution filters after adding oxolane or acetic acid ethyl dissolution after being spin-dried for, and again adds recrystallizing methanol after solvent evaporated and obtains 2-aminopyrimidine-5-boric acid pinacol ester.
A kind of method preparing 2-aminopyrimidine-5-boric acid pinacol ester, it is characterised in that: in described second step, the mol ratio of described n-BuLi Yu n-BuMgBr is 2:1；Described 2-chloro-5-Bromopyrimidine and n-Bu3The mol ratio of MgLi, methoxyl group boric acid pinacol ester or isopropoxy boric acid pinacol ester is 1:0.4-0.5:1.1-1.5.
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