CN102863435B - 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole formaldehyde and preparation method of reduction product thereof - Google Patents
2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole formaldehyde and preparation method of reduction product thereof Download PDFInfo
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 title abstract description 15
- 230000009467 reduction Effects 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 9
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 7
- 239000002841 Lewis acid Substances 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 150000007517 lewis acids Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- 238000006206 glycosylation reaction Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000006722 reduction reaction Methods 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000007037 hydroformylation reaction Methods 0.000 abstract 2
- LWBHYZBRERKAKK-UHFFFAOYSA-N N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-(1,3-thiazol-2-yl)pyridin-2-amine Chemical compound FC1=C(C=C(C=C1)NC1=NC=CC(=C1)C=1SC=CN1)C(F)(F)F LWBHYZBRERKAKK-UHFFFAOYSA-N 0.000 abstract 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 abstract 1
- 239000012279 sodium borohydride Substances 0.000 abstract 1
- 229910000033 sodium borohydride Inorganic materials 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- -1 1-(6-amino-3-pyridyl) ethyl Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000007039 two-step reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 2
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DQFULIZRFTYWLU-UHFFFAOYSA-N 2-pyridin-1-ium-4-ylacetaldehyde;bromide Chemical compound [Br-].O=CCC1=CC=[NH+]C=C1 DQFULIZRFTYWLU-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 1
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
Abstract
The invention discloses a 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole formaldehyde and a preparation method of a reduction product thereof. The preparation method is characterized by including the steps: using 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl thiazole and paraformaldehyde as raw materials to prepare the 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole formaldehyde by means of one-step hydroformylation reaction; and enabling the prepared 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole formaldehyde to react with NaBH4, so that the reduction product of the 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole formaldehyde, namely, 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole methanol is prepared. The preparation method adopting the one-step hydroformylation reaction is simple in reaction process, high in yield and good in environmental friendliness.
Description
Technical field:
The present invention relates to the preparation method of a kind of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde and reduzate thereof, belong to chemosynthesis technical field.
Background technology:
α
7nAChR (nAChRs) is a class five yuan of ligand-gated ion channels, is extensively distributed in neural system and (comprises pallium and hippocampus).The nAChRs of activation causes the inward electric current of a rapid deactivation, and it mainly enters activating cells kinases by calcium channel, and further pharmacological research shows, activates α
7passage improves cognitive performance, comprises the disappearance of attention, study, working memory, cognitive handiness.2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole derivative is a kind of α of novel highly selective
7nAChR.Patent WO03015773A2, WO2007031440A2 report this compounds as a kind of novel α
7the effect of nAChR in relative disease.
The method of synthesis 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] the is amino]-4-pyridyl-5-thiazole methyl alcohol that document WO2007031440A2 reports is obtained by reacting 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole with 1-(6-amino-3-pyridyl) ethyl ketone and 1-(the fluoro-3-of 4-(trifluoromethyl) phenyl) thiocarbamide, then bromination is passed through, pass through at-78 DEG C again and butyllithium reaction, aldehyde radical product 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde is obtained after adding DMF again, and then reduction obtains target product under lithium aluminium hydride, wherein need bromo activation in advance before aldehyde glycosylation reaction, and reaction needed is carried out at low temperatures, the overall yield of two-step reaction is about 55%, in reaction bromo again debrominate produce a large amount of pollutions.A kind of other route of synthesis is reported in patent WO2009114552A1,2-[(3-aminomethyl phenyl) is amino]-4-pyridyl-5-thiazole carboxaldehyde can be directly obtained with formaldehyde reaction, then reaction can not be changed completely, 2-[(3-aminomethyl phenyl) is amino]-4-pyridyl-5-thiazole carboxaldehyde can be obtained subsequently through manganese dioxide, wherein need the oxygenant using 7 times of molar weights.The overall yield of two-step reaction is about 30%.
Based on the above-mentioned situation of prior art, applicant makes the present invention.
Summary of the invention:
A first aspect of the present invention object is to provide that a kind of reaction process is simple and the preparation method of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] the is amino]-4-pyridyl-5-thiazole carboxaldehyde that reaction yield is high, the feature of environmental protection is good.
The technical scheme that the present invention takes for achieving the above object is as follows:
The preparation method of a kind of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that, comprise the following steps: with 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] amino]-4-pyridyl thiazole and paraformaldehyde for raw material, a step aldehyde glycosylation reaction prepares 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde.
Further setting is:
In reaction:
The mol ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and paraformaldehyde is 1:5 ~ 15.
The mol ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and paraformaldehyde is 1:5 ~ 10.
Described reaction is carried out in the presence of the solvent, and solvent is selected from acetonitrile or ethanolic soln.
Described reaction is carried out in the presence of base, and the alkali of use is triethylamine, diethylamine or Pyrrolidine.Be preferably triethylamine, the amount of substance ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and alkali is 1:2 ~ 5.
Described reaction is carried out in the presence of a lewis acid, and Lewis acid is magnesium chloride, zinc chloride, iron(ic) chloride or aluminum chloride.
Described Lewis acid is magnesium chloride, and the amount of substance ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and magnesium chloride is 1:1.
A second aspect of the present invention object is to provide the method that a kind of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde prepares its reduzate, it is characterized in that: by 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] the is amino]-4-pyridyl-5-thiazole carboxaldehyde of preparation and NaBH
4reaction, the reduzate of preparation 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde and 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol.
Further: 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde and NaBH
4mol ratio be 3:1, reduction reaction is carried out in methanol solution, room temperature reaction 2 hours, be extracted with ethyl acetate, after anhydrous magnesium sulfate drying product 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol.
Principle of the present invention and the chemical reaction process related to as follows:
Reaction mechanism: the present invention with 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] amino]-4-pyridyl thiazole for raw material, by directly carrying out single stage method aldehyde glycosylation reaction with paraformaldehyde, prepare 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, and then obtain 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol by reduction.Wherein: the productive rate of single stage method aldehyde glycosylation reaction is 76%, and the productive rate (55%) reacted than existing two-step approach significantly improves, and can reduce the environmental pollution that in two-step reaction, bromo-reaction brings.
The chemical equation that the present invention relates to:
In above-mentioned reaction formula:
Formula 1 is 1-(the fluoro-3-of 4-(trifluoromethyl) phenyl) thiocarbamide, hereinafter referred to as compound 1.
Formula 2 is the bromo-1-of 2-(4-pyridyl) ethanone hydrobromide, hereinafter referred to as compound 2.
Formula 3 is 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole, hereinafter referred to as compound 3.
Formula 4 is 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, hereinafter referred to as compound 4.
Formula 5 is 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol, hereinafter referred to as compound 5.
Below in conjunction with the drawings and specific embodiments, the invention will be further described.
Accompanying drawing illustrates:
Fig. 1 be compound 4 (
1h NMR, 400M, solvent DMSO) nuclear magnetic resonance map;
Fig. 2 be compound 5 (
1h NMR, 400M, solvent DMSO) nuclear magnetic resonance map.
Embodiment:
The synthesis of embodiment 1, compound 3.
By compound 1 (43 g, 0.18 mol) and compound 2 (60.7 g, 0.216 mol) to be dissolved in the ethanol of 2L stirring and refluxing 4 hours, then room temperature is cooled to, concentrated, residuum is poured in saturated sodium carbonate solution, filter, and with 100mL water washing three times, vacuum-drying obtains brown solid 54 g, productive rate 88%.
The synthesis of embodiment 2, compound 4.
By compound 3(0.1mol, 33.9g) be dissolved in the acetonitrile solution of 100mL, add paraformaldehyde (1mol under stirring, 30g), triethylamine (0.35mol, 35.3g), with magnesium chloride (0.1mol, 9.5g), then reflux 2 hours, TLC controls reaction end, and reclaim under reduced pressure major part acetonitrile, is poured in the dilute hydrochloric acid of 5% of 300mL by reaction solution, then extracted with diethyl ether (4 × 100 mL) is used, anhydrous magnesium sulfate drying, the concentrated solid product (28 g, productive rate 76%) obtaining yellow.
The synthesis of embodiment 3, compound 5.
NaBH
4(2.27 g, 60 mmol) slowly join in the 400mL methanol solution of compound 4 (7.35 g 20 mmol) under room temperature, reaction stirring at room temperature 2 hours, point sample determination reaction end, is then poured into reaction solution in 300mL water, is extracting by ethyl acetate (5 × 200 mL), use saturated common salt water washing respectively again, anhydrous magnesium sulfate drying, the concentrated solid product (6.43 g, productive rate 87%) obtaining yellow.
Claims (2)
1. the preparation method of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that, comprise the following steps: with 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] amino]-4-pyridyl thiazole and paraformaldehyde for raw material, a step aldehyde glycosylation reaction prepares 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde;
The mol ratio of described 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and paraformaldehyde is 1:5 ~ 15;
Described reaction is carried out in the presence of the solvent, and solvent is selected from acetonitrile or ethanolic soln;
Described reaction is carried out in the presence of base, and the alkali of use is triethylamine, diethylamine or Pyrrolidine;
Described reaction is carried out in the presence of a lewis acid, and Lewis acid is magnesium chloride, zinc chloride, iron(ic) chloride or aluminum chloride.
2. the preparation method of a kind of 2-according to claim 1 [[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, is characterized in that: the mol ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and paraformaldehyde is 1:5 ~ 10.
3. the preparation method of a kind of 2-according to claim 1 [[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described alkali is triethylamine, the amount of substance ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and alkali is 1:2 ~ 5.
4. the preparation method of a kind of 2-according to claim 1 [[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described Lewis acid is magnesium chloride, the amount of substance ratio of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl thiazole and magnesium chloride is 1:1.
5. the preparation method of 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol, it is characterized in that: prepare 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde according to any one of claim 1-4 preparation method, then by 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] the is amino]-4-pyridyl-5-thiazole carboxaldehyde of preparation and NaBH
4reaction, the reduzate of preparation 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde and 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol.
6. the preparation method of a kind of 2-according to claim 5 [[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol, is characterized in that: 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole carboxaldehyde and NaBH
4mol ratio be 3:1, reduction reaction is carried out in methanol solution, room temperature reaction 2 hours, be extracted with ethyl acetate, after anhydrous magnesium sulfate drying product 2-[[the fluoro-3-of 4-(trifluoromethyl) phenyl] is amino]-4-pyridyl-5-thiazole methyl alcohol.
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| DE10038436A1 (en) * | 2000-08-07 | 2002-03-28 | Siemens Ag | New 5-acceptor-functionalized 2-diarylamino thiophene or thiazole derivatives, especially useful for making organic light-emitting diodes |
| CN1541097A (en) * | 2001-08-13 | 2004-10-27 | ղɭҩҵ����˾ | 2-amino-4, 5-trisubstituted thiazolyl derivatives |
| WO2007031440A2 (en) * | 2005-09-13 | 2007-03-22 | Janssen Pharmaceutica N.V. | 2-aniline-4-aryl substituted thiazole derivatives |
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