CN102863435A - 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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- CN102863435A CN102863435A CN2012103588270A CN201210358827A CN102863435A CN 102863435 A CN102863435 A CN 102863435A CN 2012103588270 A CN2012103588270 A CN 2012103588270A CN 201210358827 A CN201210358827 A CN 201210358827A CN 102863435 A CN102863435 A CN 102863435A
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 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 30
- 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
- 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 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- NJPWEWURYDJIOJ-UHFFFAOYSA-N 2-pyridin-4-yl-1,3-thiazole-5-carbaldehyde Chemical compound S1C(C=O)=CN=C1C1=CC=NC=C1 NJPWEWURYDJIOJ-UHFFFAOYSA-N 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound 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
- -1 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde Chemical compound 0.000 claims description 11
- ISISZAZLEGLXEO-UHFFFAOYSA-N 2-pyridin-4-yl-1,3-thiazole Chemical compound C1=CSC(C=2C=CN=CC=2)=N1 ISISZAZLEGLXEO-UHFFFAOYSA-N 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 7
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000002841 Lewis acid Substances 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
- 150000001299 aldehydes Chemical class 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
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- 238000007348 radical reaction 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
- 230000002378 acidificating effect Effects 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 238000003810 ethyl acetate extraction Methods 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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 8
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000007037 hydroformylation reaction Methods 0.000 abstract 2
- 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
- 150000001875 compounds Chemical class 0.000 description 5
- 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-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
- 230000002194 synthesizing effect Effects 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
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 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
- 238000005481 NMR spectroscopy Methods 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
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 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
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 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
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- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
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- 229940125904 compound 1 Drugs 0.000 description 1
- 230000009849 deactivation Effects 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
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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 a kind of 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde and reduzate thereof, belong to chemosynthesis technical field.
Background technology:
α
7NAChR (nAChRs) is five yuan of part gated ion channels of a class, extensively is distributed in the neural system (to comprise pallium and hippocampus).The nAChRs of activation causes the inward electric current of a rapid deactivation, and it mainly is to enter the 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-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole derivative is a kind of α of novel highly selective
7NAChR.Patent WO03015773A2, WO2007031440A2 have reported that this compounds is as a kind of novel α
7The effect of nAChR in relative disease.
Synthetic 2-[[4-fluoro-3-(trifluoromethyl) phenyl of document WO 2007031440A2 report] amino]-method of 4-pyridyl-5-thiazole methyl alcohol is to obtain 2-[[4-fluoro-3-(trifluoromethyl) phenyl with 1-(6-amino-3-pyridyl) ethyl ketone and the reaction of 1-(4-fluoro-3-(trifluoromethyl) phenyl) thiocarbamide] amino]-the 4-pyridyl thiazole, then pass through bromination, lower to reacting with butyllithium at-78 ℃ again, obtain aldehyde radical product 2-[[4-fluoro-3-(trifluoromethyl) phenyl after adding again DMF] amino]-4-pyridyl-5-thiazole carboxaldehyde, and then reduction obtains target product under lithium aluminium hydride, wherein need in advance bromo activation before the aldehyde radical reaction, and reaction needed is carried out at low temperatures, the overall yield of two-step reaction about 55%, in the reaction bromo again debrominate produce a large amount of pollutions.Reported a kind of other route of synthesis among the patent WO2009114552A1, can directly obtain the 2-[(3-aminomethyl phenyl with formaldehyde reaction) amino]-4-pyridyl-5-thiazole carboxaldehyde, then reaction can not be changed fully, follow-uply can obtain the 2-[(3-aminomethyl phenyl by the Manganse Dioxide oxidation) amino]-4-pyridyl-5-thiazole carboxaldehyde, wherein need to use the oxygenant of 7 times of molar weights.The overall yield of two-step reaction is about 30%.
Based on the above-mentioned situation of prior art, the applicant makes the present invention.
Summary of the invention:
A first aspect of the present invention purpose provides 2-[[4-fluoro-3-(trifluoromethyl) phenyl that a kind of reaction process is simple and reaction yield is high, the feature of environmental protection is good] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde.
The technical scheme that the present invention takes for achieving the above object is as follows:
A kind of 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that, may further comprise the steps: take 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl thiazole and Paraformaldehyde 96 are as raw material, and step aldehyde radical reaction prepares 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde.
Further arrange and be:
In the reaction:
2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-mol ratio of 4-pyridyl thiazole and Paraformaldehyde 96 is 1:5 ~ 15.
2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-mol ratio of 4-pyridyl thiazole and Paraformaldehyde 96 is 1:5 ~ 10.
Described reaction is carried out in the presence of solvent, and solvent is selected from acetonitrile or ethanolic soln.
Described reaction is carried out in the presence of alkali, and the alkali that uses is triethylamine, diethylamine or Pyrrolidine.Be preferably triethylamine, 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-molar ratio of 4-pyridyl thiazole and alkali is 1:2 ~ 5.
Described reaction is carried out in the presence of lewis acidic, and Lewis acid is magnesium chloride, zinc chloride, iron(ic) chloride or aluminum chloride.
Described Lewis acid is magnesium chloride, 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-molar ratio of 4-pyridyl thiazole and magnesium chloride is 1:1.
A second aspect of the present invention purpose provides a kind of 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde prepares the method for its reduzate, it is characterized in that: with 2-[[4-fluoro-3-(trifluoromethyl) phenyl of preparation] and amino]-4-pyridyl-5-thiazole carboxaldehyde and NaBH
4Reaction, preparation 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-reduzate of 4-pyridyl-5-thiazole carboxaldehyde is 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole methyl alcohol.
Further: 2-[[4-fluoro-3-(trifluoromethyl) phenyl] 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, with behind the ethyl acetate extraction, anhydrous magnesium sulfate drying product 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole methyl alcohol.
Principle of the present invention and the chemical reaction process that relates to are as follows:
Reaction mechanism: the present invention is take 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-the 4-pyridyl thiazole is as raw material, by directly carrying out the reaction of single stage method aldehyde radical with Paraformaldehyde 96, prepare 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde, and then obtain 2-[[4-fluoro-3-(trifluoromethyl) phenyl by reduction] amino]-4-pyridyl-5-thiazole methyl alcohol.Wherein: the productive rate of single stage method aldehyde radical reaction than the obviously raising of productive rate (55%) of existing two-step approach reaction, and can reduce the environmental pollution that bromo-reaction brings in the two-step reaction 76%.
The chemical equation that the present invention relates to:
In the above-mentioned reaction formula:
Formula 1 is 1-(4-fluoro-3-(trifluoromethyl) phenyl) thiocarbamide, hereinafter referred to as compound 1.
Formula 2 is 2-bromo-1-(4-pyridyl) ethyl ketone hydrobromate, hereinafter referred to as compound 2.
Formula 4 is 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde, hereinafter referred to as compound 4.
Formula 5 is 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole methyl alcohol, hereinafter referred to as compound 5.
The invention will be further described below in conjunction with the drawings and specific embodiments.
Description of drawings:
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:
Synthesizing of embodiment 1, compound 3.
With compound 1 (43 g, 0.18 mol) with compound 2 (60.7 g, 0.216 mol) be dissolved in the ethanol of 2L stirring and refluxing 4 hours, then be cooled to room temperature, concentrated, residuum is poured in the saturated sodium carbonate solution, filter, and with 100mL water washing three times, vacuum-drying obtains brown solid 54 g, productive rate 88%.
Synthesizing of embodiment 2, compound 4.
With compound 3(0.1mol, 33.9g) be dissolved in the acetonitrile solution of 100mL, stir the lower Paraformaldehyde 96 (1mol that adds, 30g), triethylamine (0.35mol, 35.3g), and magnesium chloride (0.1mol, 9.5g), then refluxed 2 hours, TLC controls reaction end, and the most of acetonitrile of reclaim under reduced pressure is poured into reaction solution in 5% the dilute hydrochloric acid of 300mL, then use extracted with diethyl ether (4 * 100 mL), anhydrous magnesium sulfate drying, the concentrated solid product (28 g, productive rate 76%) that obtains yellow.
Synthesizing of embodiment 3, compound 5.
NaBH
4(2.27 g, 60 mmol) slowly join under the room temperature in the 400mL methanol solution of compound 4 (7.35 g, 20 mmol), the reaction stirring at room is about 2 hours, point sample is determined reaction end, then reaction solution is poured in the 300mL water, is extracting with ethyl acetate (5 * 200 mL), use respectively again the saturated common salt water washing, anhydrous magnesium sulfate drying, the concentrated solid product (6.43 g, productive rate 87%) that obtains yellow.
Claims (10)
1. a 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that, may further comprise the steps: take 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl thiazole and Paraformaldehyde 96 are as raw material, and step aldehyde radical reaction prepares 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde.
2. a kind of 2-[[4-fluoro-3-according to claim 1 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-mol ratio of 4-pyridyl thiazole and Paraformaldehyde 96 is 1:5 ~ 15.
3. a kind of 2-[[4-fluoro-3-according to claim 1 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-mol ratio of 4-pyridyl thiazole and Paraformaldehyde 96 is 1:5 ~ 10.
4. a kind of 2-[[4-fluoro-3-according to claim 1 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described reaction is carried out in the presence of solvent, and solvent is selected from acetonitrile or ethanolic soln.
5. a kind of 2-[[4-fluoro-3-according to claim 1 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described reaction is carried out in the presence of alkali, and the alkali that uses is triethylamine, diethylamine or Pyrrolidine.
6. a kind of 2-[[4-fluoro-3-according to claim 5 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described alkali is triethylamine, 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-molar ratio of 4-pyridyl thiazole and alkali is 1:2 ~ 5.
7. a kind of 2-[[4-fluoro-3-according to claim 1 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described reaction is carried out in the presence of lewis acidic, and Lewis acid is magnesium chloride, zinc chloride, iron(ic) chloride or aluminum chloride.
8. a kind of 2-[[4-fluoro-3-according to claim 7 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde, it is characterized in that: described Lewis acid is magnesium chloride, 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-molar ratio of 4-pyridyl thiazole and magnesium chloride is 1:1.
9.
A kind of 2-[[4-fluoro-3-(trifluoromethyl) phenyl of each preparation of claim 1-8] amino]-4-pyridyl-5-thiazole carboxaldehyde prepares the method for its reduzate, it is characterized in that: with 2-[[4-fluoro-3-(trifluoromethyl) phenyl of preparation] and amino]-4-pyridyl-5-thiazole carboxaldehyde and NaBH 4 Reaction, preparation 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-reduzate of 4-pyridyl-5-thiazole carboxaldehyde is 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole methyl alcohol.
10.
A kind of 2-[[4-fluoro-3-according to claim 9 (trifluoromethyl) phenyl] amino]-preparation method of 4-pyridyl-5-thiazole carboxaldehyde reduzate, it is characterized in that: 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole carboxaldehyde and NaBH 4 Mol ratio be 3:1, reduction reaction is carried out in methanol solution, room temperature reaction 2 hours, with behind the ethyl acetate extraction, anhydrous magnesium sulfate drying product 2-[[4-fluoro-3-(trifluoromethyl) phenyl] amino]-4-pyridyl-5-thiazole methyl alcohol.
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