CN106632443A - Synthesis method of 2-aminopyrimidine-5-boronic acid pinacol ester borate - Google Patents
Synthesis method of 2-aminopyrimidine-5-boronic acid pinacol ester borate Download PDFInfo
- Publication number
- CN106632443A CN106632443A CN201611037327.1A CN201611037327A CN106632443A CN 106632443 A CN106632443 A CN 106632443A CN 201611037327 A CN201611037327 A CN 201611037327A CN 106632443 A CN106632443 A CN 106632443A
- Authority
- CN
- China
- Prior art keywords
- aminopyrimidine
- ester
- frequency
- amino
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- CSMZYNOVXYBFOX-UHFFFAOYSA-N B(O)(O)O.NC1=NC=C(C=N1)B1OC(C)(C)C(C)(C)O1 Chemical compound B(O)(O)O.NC1=NC=C(C=N1)B1OC(C)(C)C(C)(C)O1 CSMZYNOVXYBFOX-UHFFFAOYSA-N 0.000 title abstract 4
- 238000001308 synthesis method Methods 0.000 title abstract 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 33
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 235000011056 potassium acetate Nutrition 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims abstract description 3
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims abstract description 3
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims abstract description 3
- 238000001953 recrystallisation Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 17
- 238000010189 synthetic method Methods 0.000 claims description 14
- -1 ester borate Chemical class 0.000 claims description 12
- 150000005721 2-amino-5-bromopyrimidines Chemical class 0.000 claims description 11
- 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 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 34
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- UHRHPPKWXSNZLR-UHFFFAOYSA-N 5-bromopyrimidin-2-amine Chemical compound NC1=NC=C(Br)C=N1 UHRHPPKWXSNZLR-UHFFFAOYSA-N 0.000 abstract 3
- 230000035484 reaction time Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 238000000034 method Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 11
- SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000010009 beating Methods 0.000 description 5
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical group NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 3
- 239000000052 vinegar Substances 0.000 description 3
- 235000021419 vinegar Nutrition 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 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
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 241000252233 Cyprinus carpio Species 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 240000000233 Melia azedarach Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000233855 Orchidaceae Species 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 229950004111 apitolisib Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 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
- 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
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000011160 research 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
- C07F5/04—Esters of boric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of 2-aminopyrimidine-5-boronic acid pinacol ester borate. The synthesis method comprises the following steps: carrying out continuous reaction at the temperature of 50 to 125 DEG C for 3 to 8 hours on 2-amino-5-bromopyrimidine and bisdiboron which serve as raw materials in a proper solvent under the action of specific alkaline potassium acetate and 1,1'-dis(diphenylphosphine) ferrocene] palladium dichloride dichloromethane complex serving as a specific catalyst to generate a 2-aminopyrimidine-5-boronic acid pinacol ester borate coarse product, wherein the amount ratio of the 2-amino-5-bromopyrimidine to the bisdiboron is 1 to (0.95 to 2.1), and the amount ratio of the 2-amino-5-bromopyrimidine to the solvent is 1 to (4.0 to 30); carrying out recrystallization to obtain a 2-aminopyrimidine-5-boronic acid pinacol ester borate pure product. According to the synthesis method, the raw material is relatively easy to obtain, and the operation is easy; the specific alkali and the specific catalyst accelerate the reaction progress and shortens the reaction time; the reaction yield is high, and the purity is high.
Description
(One)Technical field
The invention belongs to organic synthesis field, more particularly to a kind of 2- aminopyrimidine-5-boric acids frequency any ester boratory synthesis side
Method.
(Two)Background technology
List or the I types PI3K inhibitor Apitolisib and kinase inhibitor Votrient in new drug is ground known, all contain
Have a 2- aminopyrimidine groups, and have more researchs will this fragment as important construction unit.2- aminopyrimidine -5- boron
Sour which ester of frequency is disclosed at present the synthetic method of data as one of key intermediate:It is main to include 1)Using 2- ammonia
Base -5- iodine pyrimidines are with pinacol borine in the case where being catalyzed in Pd (PPh) 4(With reference to: Org. Biomol.Chem. ,2011,9,
3139)Or the Ao Lve institutes of 2 one amino -5 one are intended to be coupled in the presence of PdCl2dppf with Lian Pengsuan pinacols state(With reference to: WO
2012/109423 Al) ;2)Using same raw material by amino Boe(With reference to:CN102399235A and
CN102367260A)Or diphenyl methylene(With reference to: US 2008/0269523 Al )After protection,(Or do not protect directly, ginseng
Examine: Eur.J.Org.Chem. 2007,5712)It is initially formed using ultralow temperature reaction at I bases Cyprinus carpio/78 DEG C of canopy acid orchid isopropyl vinegar I
Canopy acid, after subsequent deprotection, followed by with pinacol vinegar is reacted into.Said method: 1 )Coupling catalyst large usage quantity, cost
Height, and product has heavy-metal residual: 2)Amino cannot contract using during the intoxicated protection of hexichol first according to the patented method first step
Product is closed, needs are with nitrogen is all protected when protect using Boe:Amino does not protect the method yield of direct reaction unstable
Determine, poor reproducibility, and such method all haves the shortcomings that to need ultralow temperature to react.
(Three)The content of the invention
The present invention is in order to make up the deficiencies in the prior art, there is provided a kind of 2- aminopyrimidine-5-boric acids frequency is which boratory conjunction of ester
Into method.
The present invention is achieved through the following technical solutions:
A kind of 2- aminopyrimidine-5-boric acids frequency is which boratory synthetic method of ester, it is characterised in that:Comprise the following steps:With 2-
Amino -5- Bromopyrimidines and connection boric acid pinacol ester are raw material, in solvent and catalyst, in the presence of alkali, in 50-125 DEG C of reaction
3-8 hour generates 2- aminopyrimidine-5-boric acids which ester borate frequently, and then Jing is recrystallized to give sterling 2- aminopyrimidine -5-
Boric acid frequency is which ester borate.
The 2- aminopyrimidine-5-boric acids frequency of the present invention is which boratory synthetic method of ester, it is characterised in that:The solvent is
One or two in dichloromethane, ethanol, 1,4- dioxane, acetonitrile, methanol and DMF.
The 2- aminopyrimidine-5-boric acids frequency of the present invention is which boratory synthetic method of ester, it is characterised in that:The alkali is vinegar
Sour potassium.
The 2- aminopyrimidine-5-boric acids frequency of the present invention is which boratory synthetic method of ester, it is characterised in that:The catalyst
It is double (diphenylphosphine) ferrocene of 1,1'-] palladium chloride dichloromethane complex
The 2- aminopyrimidine-5-boric acids frequency of the present invention is which boratory synthetic method of ester, it is characterised in that:The reactant with it is molten
The inventory of agent is:2- amino -5- Bromopyrimidines:Solvent=1:4 ~ 30, the above is weight ratio.
The 2- aminopyrimidine-5-boric acids frequency of the present invention is which boratory synthetic method of ester, it is characterised in that:The purification step
Suddenly it is evaporation and concentration, recrystallization.
Which boratory synthesis technique of ester of 2- aminopyrimidine-5-boric acids frequency of the present invention and synthesis step are as follows:
The invention has the beneficial effects as follows:2- aminopyrimidine-5-boric acids which ester borate frequently is prepared using the present invention, is urged using specific
Agent and specific alkali, reaction condition is gentle, and operation is simple, and product quality is stable, and purity is high.
(Four)Specific embodiment
Embodiment 1:
2- amino -5- Bromopyrimidines are added in 100mL three neck round bottom flask(1.044g, 6mmol), connection boric acid pinacol ester
(1.524g, 6mmol), acetonitrile 30ml, potassium acetate(1.767g, 18mmol), Pd (dppf) Cl2.CH2Cl2(0.245g,
0.3mmol).Mixture in reaction bulb stirring reaction 7 hours at 85 DEG C.TLC and HPLC determine that reaction is completed.Reaction terminates
Afterwards, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 beating, then re-crystallizing in ethyl acetate is obtained
To net product 2- aminopyrimidine-5-boric acids frequency any ester borate, after being dried, calculated yield 64.73%, purity 98.76% (HPLC),
Nuclear magnetic resonance spectroscopy:1HNMR (400Hz, deuterated DMSO) δ:1.16 (s, 12H), 1.27 (s, 12H), 7.03 (s, 2H), 7.94
(s,1H), 8.37(s, 2H)。
Embodiment 2:
2- amino -5- Bromopyrimidines are added in 100mL three neck round bottom flask(1.044g, 6mmol), connection boric acid pinacol ester
(1.905g, 7.5mmol), acetonitrile 30ml, potassium acetate(1.767g, 18mmol), Pd (dppf) Cl2.CH2Cl2(0.245g,
0.3mmol).Mixture in reaction bulb stirring reaction 7 hours at 85 DEG C.TLC and HPLC determine that reaction is completed.Reaction terminates
Afterwards, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 beating, then re-crystallizing in ethyl acetate is obtained
To net product 2- aminopyrimidine-5-boric acids frequency any ester borate, after being dried, calculated yield 78.49%, purity 99.00% (HPLC).
Embodiment 3:
2- amino -5- Bromopyrimidines are added in 100mL three neck round bottom flask(1.044g, 6mmol), connection boric acid pinacol ester
(1.905g, 7.5mmol), DMF 30ml, potassium acetate(1.767g, 18mmol), Pd (dppf) Cl2.CH2Cl2(0.245g,
0.3mmol).Mixture in reaction bulb stirring reaction 7 hours at 85 DEG C.TLC and HPLC determine that reaction is completed.Reaction terminates
Afterwards, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 beating, then re-crystallizing in ethyl acetate is obtained
To net product 2- aminopyrimidine-5-boric acids frequency any ester borate, after being dried, calculated yield 68%, the % of purity 99.00 (HPLC).
Embodiment 4:
2- amino -5- Bromopyrimidines are added in 100mL three neck round bottom flask(1.044g, 6mmol), connection boric acid pinacol ester
(3.048g, 12mmol), DMF 30ml, potassium acetate(1.767g, 18mmol), Pd (dppf) Cl2.CH2Cl2(0.245g,
0.3mmol).Mixture in reaction bulb stirring reaction 6.5 hours at 85 DEG C.TLC and HPLC determine that reaction is completed.Reaction knot
Shu Hou, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 are beaten, then re-crystallizing in ethyl acetate
Net product 2- aminopyrimidine-5-boric acids any ester borate frequently is obtained, after being dried, calculated yield 60.47%, the % of purity 98.71
(HPLC)。
Embodiment 5:
2- amino -5- Bromopyrimidines are added in 500mL three neck round bottom flask(10.44g, 60mmol), connection boric acid pinacol ester
(19.05g, 75mmol), acetonitrile 300ml, potassium acetate(17.67g, 180mmol), Pd (dppf) Cl2.CH2Cl2(2.45g,
3mmol).Mixture in reaction bulb stirring reaction 6.5 hours at 85 DEG C.TLC and HPLC determine that reaction is completed.Reaction terminates
Afterwards, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 beating, then re-crystallizing in ethyl acetate is obtained
To net product 2- aminopyrimidine-5-boric acids frequency any ester borate, after being dried, calculated yield 80%, the % of purity 99.45 (HPLC).
Embodiment 6
2- amino -5- Bromopyrimidines are added in 500mL three neck round bottom flask(10.44g, 60mmol), connection boric acid pinacol ester
(19.05g, 75mmol), methanol 310ml, potassium acetate(17.67g, 180mmol), Pd (dppf) Cl2.CH2Cl2(2.45g,
3mmol).Mixture in reaction bulb stirring reaction 6.5 hours at 85 DEG C.TLC and HPLC determine that reaction is completed.Reaction terminates
Afterwards, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 beating, then re-crystallizing in ethyl acetate is obtained
To net product 2- aminopyrimidine-5-boric acids frequency any ester borate, after being dried, calculated yield 62%, purity 98.24% (HPLC).
Embodiment 7
2- amino -5- Bromopyrimidines are added in 3L three neck round bottom flask(87g, 500mmol), connection boric acid pinacol ester
(158.75g, 625mmol), acetonitrile 1500ml, potassium acetate(147.21g, 1500mmol), Pd (dppf) Cl2.CH2Cl2
(20.375g, 25mmol).Mixture in reaction bulb stirring reaction 6.5 hours at 85 DEG C.TLC and HPLC determinations have been reacted
Into.After reaction terminates, revolving removes solvent, obtains crude product, crude product dichloromethane:Normal hexane=1:3 are beaten, then acetic acid
Ethyl ester is recrystallized to give net product 2- aminopyrimidine-5-boric acids which ester borate frequently, after being dried, calculated yield 78.36%, and purity
98.17%(HPLC)。
The present invention illustrates the detailed process equipment of the present invention and technological process by above-mentioned case study on implementation, but the present invention is simultaneously
Above-mentioned detailed process equipment and technological process are not limited only to, that is, do not mean that the present invention has to rely on above-mentioned detailed process equipment
Could implement with technological process.The those skilled in the art it will be clearly understood that any improvement in the present invention, to the present invention
The equivalence replacement of each raw material of product and the addition of auxiliary element, the selection of concrete mode etc., all fall within protection scope of the present invention
Within the scope of disclosure.
Claims (6)
1. a kind of 2- aminopyrimidine-5-boric acids frequency any ester boratory synthetic method, it is characterised in that:Comprise the following steps:With
2- amino -5- Bromopyrimidines and connection boric acid pinacol ester are raw material, anti-at 50-125 DEG C in the presence of alkali in solvent and catalyst
Answer 3-8 hour generates 2- aminopyrimidine-5-boric acids frequency which ester borate, then Jing be recrystallized to give sterling 2- aminopyrimidine-
5- boric acid frequency is which ester borate.
2. 2- aminopyrimidine-5-boric acids according to claim 1 frequency any ester boratory synthetic method, it is characterised in that:
The solvent is one or two in dichloromethane, ethanol, 1,4- dioxane, acetonitrile, methanol and DMF.
3. which boratory synthetic method of ester of 2- aminopyrimidine-5-boric acids according to claim 1 and 2 frequency, its feature exists
In:The alkali is potassium acetate.
4. which boratory synthetic method of ester of 2- aminopyrimidine-5-boric acids according to claim 1 and 2 frequency, its feature exists
In:The catalyst is double (diphenylphosphine) ferrocene of 1,1'-] palladium chloride dichloromethane complex.
5. which boratory synthetic method of ester of 2- aminopyrimidine-5-boric acids according to claim 1 and 2 frequency, its feature exists
In:The reactant is with the inventory of solvent:2- amino -5- Bromopyrimidines:Solvent=1:4 ~ 30, the above is weight ratio.
6. which boratory synthetic method of ester of 2- aminopyrimidine-5-boric acids according to claim 1 and 2 frequency, its feature exists
In:The purification step be evaporation and concentration, recrystallization.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611037327.1A CN106632443B (en) | 2016-11-23 | 2016-11-23 | Synthesis method of 2-aminopyrimidine-5-boric acid pinacol borate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611037327.1A CN106632443B (en) | 2016-11-23 | 2016-11-23 | Synthesis method of 2-aminopyrimidine-5-boric acid pinacol borate |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106632443A true CN106632443A (en) | 2017-05-10 |
CN106632443B CN106632443B (en) | 2022-06-17 |
Family
ID=58811079
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201611037327.1A Active CN106632443B (en) | 2016-11-23 | 2016-11-23 | Synthesis method of 2-aminopyrimidine-5-boric acid pinacol borate |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106632443B (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103467482A (en) * | 2012-04-10 | 2013-12-25 | 上海昀怡健康管理咨询有限公司 | Condensed pyrimidine compound, and preparation method, intermediate, composition and application thereof |
CN103476765A (en) * | 2011-02-11 | 2013-12-25 | 达娜-法勃肿瘤研究所公司 | Method of inhibiting hamartoma tumor cells |
-
2016
- 2016-11-23 CN CN201611037327.1A patent/CN106632443B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103476765A (en) * | 2011-02-11 | 2013-12-25 | 达娜-法勃肿瘤研究所公司 | Method of inhibiting hamartoma tumor cells |
CN103467482A (en) * | 2012-04-10 | 2013-12-25 | 上海昀怡健康管理咨询有限公司 | Condensed pyrimidine compound, and preparation method, intermediate, composition and application thereof |
Non-Patent Citations (1)
Title |
---|
NITINCHANDRA D.PATEL等: ""Development of an Efficient Synthesis of (2-Aminopyrimidin-5-yl) Boronic Acid"", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
Also Published As
Publication number | Publication date |
---|---|
CN106632443B (en) | 2022-06-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108424388B (en) | Preparation method of medicine for treating chronic anemia | |
EP3199533B1 (en) | Pyrazole compound and pharmaceutical use thereof | |
CN106478641A (en) | The novel synthesis of Rui Boxini intermediate | |
AU2013293974B2 (en) | Method for Producing 4-[5-(Pyridin-4-yl)-1H-1,2,4-Triazol-3-yl]Pyridin-2-Carbonitrile, and Intermediate thereof | |
CN106279104B (en) | A kind of process modification method preparing amber love song Ge Lieting | |
CN103288808B (en) | A kind of Ah method is for the preparation method of Buddhist nun | |
CN103619832A (en) | Process for the manufacture of dabigatran etexilate and intermediates thereof | |
CN107207519A (en) | Yi Bu replaces the preparation method of Buddhist nun | |
CN103288758B (en) | Preparation method of dacomitinib (I) | |
US9796675B1 (en) | Intermediate for synthesizing paroxetine, method for preparing the same, and uses thereof | |
CN106632443A (en) | Synthesis method of 2-aminopyrimidine-5-boronic acid pinacol ester borate | |
CN103601645A (en) | Preparation method of 1-(phenethylamino) propane-2-alcoholic compounds or salts thereof | |
TW200927094A (en) | New salts | |
CN102285912A (en) | Method for preparing N-n-butylsulfonyl-O-(4-(4-pyridyl)-butyl)-L-tyrosine alkyl ester | |
CN105732459B (en) | Pyrrole amides class compound and preparation method thereof and purposes | |
US2739984A (en) | Tetra-substituted diamino alkanes | |
CN104177209B (en) | A kind of preparation method of aryl end alkynes | |
KR102132087B1 (en) | Method for preparing azoxystrobin | |
CN101935317B (en) | Synthesizing method of 2-methyl-7-(substituted pyrimidine-4-amino)-4-(substituted piperazine-1-base) piperidine-1-base) isoindoline-1-ketone and intermediate thereof | |
JP5501054B2 (en) | Method for producing 3,3-diaminoacrylic acid (1-diphenylmethylazetidin-3-yl) ester acetate | |
CN105732597B (en) | A kind of midbody compound and the preparation method and application thereof preparing pyrrole amides class compound | |
CN103242244B (en) | Canertinib preparation method | |
CN104829470A (en) | Set of intermediate compounds used for synthesis of Ivabradine, and applications thereof | |
US2965639A (en) | New basically substituted azepine | |
CN112724001B (en) | Ivabradine chiral intermediate compound |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |