CN106588921B - A kind of synthetic method of the methyl formate of 7 azaindole 3 - Google Patents
A kind of synthetic method of the methyl formate of 7 azaindole 3 Download PDFInfo
- Publication number
- CN106588921B CN106588921B CN201710024130.2A CN201710024130A CN106588921B CN 106588921 B CN106588921 B CN 106588921B CN 201710024130 A CN201710024130 A CN 201710024130A CN 106588921 B CN106588921 B CN 106588921B
- Authority
- CN
- China
- Prior art keywords
- azaindoles
- mol
- synthetic method
- solvent
- water
- 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.)
- Expired - Fee Related
Links
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 238000010189 synthetic method Methods 0.000 title claims abstract description 25
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 title abstract 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 51
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 239000002904 solvent Substances 0.000 claims abstract description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000002585 base Substances 0.000 claims abstract description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 22
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- -1 hydroxy nitrile Chemical class 0.000 claims abstract description 11
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 229910052751 metal Inorganic materials 0.000 claims abstract description 3
- 239000002184 metal Substances 0.000 claims abstract description 3
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 claims abstract 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 111
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 28
- 239000012043 crude product Substances 0.000 claims description 24
- 239000011259 mixed solution Substances 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 18
- 238000001704 evaporation Methods 0.000 claims description 16
- 230000008020 evaporation Effects 0.000 claims description 16
- 239000012074 organic phase Substances 0.000 claims description 16
- 239000003208 petroleum Substances 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 16
- 238000000605 extraction Methods 0.000 claims description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 13
- 238000001953 recrystallisation Methods 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 11
- 150000005771 2-amino-3-bromopyridine Chemical class 0.000 claims description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 239000012265 solid product Substances 0.000 claims description 10
- 239000000725 suspension Substances 0.000 claims description 10
- MUCWDACENIACBH-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=N1 MUCWDACENIACBH-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical class CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 2
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 claims description 2
- LMHHRCOWPQNFTF-UHFFFAOYSA-N s-propan-2-yl azepane-1-carbothioate Chemical compound CC(C)SC(=O)N1CCCCCC1 LMHHRCOWPQNFTF-UHFFFAOYSA-N 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 1
- 150000004985 diamines Chemical class 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- 239000000376 reactant Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 abstract description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000004575 stone Substances 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000011091 sodium acetates Nutrition 0.000 description 2
- DNMTXRJELGPOGW-UHFFFAOYSA-N 1-methylindazole-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2N(C)N=CC2=C1 DNMTXRJELGPOGW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- WUCAGAAOOWHUCS-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-2-carbonitrile Chemical compound C1=CN=C2NC(C#N)=CC2=C1 WUCAGAAOOWHUCS-UHFFFAOYSA-N 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N acetic acid;palladium Chemical compound [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a kind of synthetic method of the methyl formate of 7 azaindole 3, belong to organic synthesis field.The present invention synthesizes 3 under sour environment using the bromopyridine of 2 amino 3 as reactant with 3 hydroxy nitrile reacting metal salts（The base amino of 3 bromopyridine 2）Acrylonitrile, 3（The base amino of 3 bromopyridine 2）Acrylonitrile, alkali, catalyst system and catalyzing are added in solvent, the reaction generation azaindole of 3 cyano group 7, the methyl formate of 7 azaindole 3 are finally reacted to obtain in the presence of methanol and hydrochloric acid.Raw material of the present invention is cheap and easy to get, and reactions steps are simple, and reaction condition is gentle, and product quality is stable, and purity is high, is adapted to industrialized production.
Description
Technical field
The invention belongs to organic synthesis field, and in particular to a kind of synthetic method of 7- azaindoles -3- methyl formates.
Background technology
7- azaindole -3- methyl formates are a kind of important nitrogen-containing heterocycle compounds, be pharmaceutical synthesis it is important in
Mesosome.Or the synthetic method expensive starting materials that the compound is now reported, or synthesis step is excessively cumbersome, total recovery is relatively low, all
Be not suitable for carrying out industrialized production.
The content of the invention
To make up the deficiencies in the prior art, the present invention provides a kind of not only suitable laboratory operation but also is adapted to industrialized production
The synthetic method of 7- azaindole -3- methyl formates.
The present invention is achieved through the following technical solutions：
A kind of synthetic method of 7- azaindoles -3- methyl formates, it, which is characterized in that, comprises the following steps：
（1）Highly basic is added in solvent orange 2 A, at 5 ~ 40 DEG C, the mixed solution of acetonitrile and Ethyl formate is added dropwise, is added dropwise
After continue the h of stirring 2 ~ 5 at room temperature and obtain 3- hydroxy nitrile metal salts, then sequentially add 2- amino -3- bromopyridines and
Acetic acid, reactant mixture stir 1 ~ 3 h at 20 ~ 40 DEG C, and reaction terminates to remove solvent orange 2 A, adds water and chloroform, the water separated
Layer merges organic phase after being extracted again with chloroform, is washed with water, anhydrous sodium sulfate drying, evaporation solvent obtains 3-（3- bromopyridine -2- bases
Amino）Acrylonitrile crude product, the crude product recrystallize to obtain white solid product with the mixed solution of ethyl acetate and petroleum ether；
（2）3-（3- bromopyridine -2- base amino）Acrylonitrile, alkali, catalyst system and catalyzing are added in solvent B, at 80 ~ 120 DEG C
15 ~ 20 h of lower reaction, reaction end are cooled to room temperature, remove solvent B, add water and ethyl acetate, the water layer separated use second again
Merge organic phase after acetoacetic ester extraction, be first washed with water and use saturated common salt water washing again, anhydrous sodium sulfate drying, evaporation solvent obtains
3- cyano-7-azaindole crude products, the crude product obtain white solid product with recrystallisation from isopropanol；
（3）3- cyano-7-azaindoles are added in the mixed liquor of finite concentration hydrochloric acid and methanol, at 60 ~ 80 DEG C
10 ~ 20 h are reacted, reaction terminates to add water, and suction filtration, filtrate are neutralized with saturated sodium bicarbonate solution, there are a large amount of solids to generate, should
Suspension is stood, and is filtered, and solid distillation water washing, 7- is recrystallized to obtain with the mixed solution of ethyl acetate and petroleum ether after drying
Azaindole -3- methyl formates.
Reaction equation is as follows：
Preferably, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（1）Middle 2-
Amino -3- bromopyridines, acetonitrile, highly basic, the mol ratio of Ethyl formate and acetic acid are 1: 1.1: 1.1: 1.1: 1.3；2- amino -3- bromines
The mass ratio of pyridine and solvent is 1:（9~12）；The volume ratio of ethyl acetate and petroleum ether is 1: 3 in recrystallization solvent.
Further, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（1）Described in it is strong
Alkali is one kind in sodium methoxide, potassium methoxide, caustic alcohol, potassium ethoxide, sodium isopropylate, potassium isopropoxide；The solvent orange 2 A be benzene, toluene,
At least one of dimethylbenzene, ethanol, isopropanol and tert-butyl alcohol.
Preferably, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（2）Middle institute
State catalyst system and catalyzing to be made up of catalyst and its part, the mol ratio of catalyst and its part is 1：（2~3）；The 3-（3- bromine pyrroles
Pyridine -2- base amino）Acrylonitrile, alkali, the mol ratio of catalyst are 1:（1~2）∶（0.001~0.1）；The 3-（3- bromopyridines -2-
Base amino）The mass ratio of acrylonitrile and solvent is 1:（10~12.5）.
Further, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（2）Described in alkali
For one kind in potassium carbonate, saleratus, sodium acetate, triethylamine and pyridine.
Further, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（2）Described in urge
Change system is the palladium chloride catalyst using dicyclohexylamine as part, the acetic acid palladium chtalyst using triethylenediamine as part
Agent, using triethylenediamine as the palladium chloride catalyst of part, using dicyclohexylamine as the palladium acetate catalyst of part, with
Triethylenediamine is as one kind in the cuprous iodide catalyst of part.
Further, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（2）Described in it is molten
Agent B is DMF, dimethyl sulfoxide (DMSO), 1-METHYLPYRROLIDONE, DMA, toluene, Isosorbide-5-Nitrae-two
At least one of the ring of oxygen six, acetonitrile and ethanol.
Preferably, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（3）Middle 3-
The mass ratio of cyano-7-azaindole, hydrochloric acid and methanol is 1:（2~4）∶（2~4）；Ethyl acetate and oil in recrystallization solvent
The volume ratio of ether is 1: 6.
Further, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（3）Described in salt
The concentration of acid is 8 mol/L, one kind in 10 mol/L, 12 mol/L.
Further, the synthetic method of a kind of 7- azaindoles -3- methyl formates of the invention, step（3）Middle filtrate is used
Saturated sodium bicarbonate solution is neutralized to pH=8, has a large amount of solids to generate, and suspension stands 3 h at 0 DEG C.
The beneficial effects of the invention are as follows：The present invention is compared with prior art, and raw material is more cheap and easy to get, and reactions steps are fairly simple,
Reaction condition is gentleer, and product quality is stable, and purity is high, has not only been adapted to laboratory operation but also has been adapted to industrialized production.
Embodiment
With reference to embodiment, the present invention is further detailed explanation.
Embodiment 1
（1）38.6 g potassium methoxides（0.55 mol）It is added in 1000 mL toluene, 22.6 g acetonitriles is added dropwise while stirring
（0.55 mol）With 40.7 g Ethyl formates（0.55 mol）Mixed solution, controlling reaction temperature be no more than 20 DEG C, drip
Finish and continue to stir 4 h at room temperature.Then 86.5 g 2- amino -3- bromopyridines are sequentially added（0.5 mol）With 39.0 g acetic acid
（0.65 mol）, reactant mixture reacts 2 h at 25 DEG C.Reaction terminates to remove solvent, adds 800 mL water and 800 mL chlorine
Imitative, the water layer separated merges organic phase after being extracted twice with chloroform, and extraction every time uses the mL of chloroform 800, is washed with water, anhydrous
Sodium sulphate is dried, and evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Acrylonitrile crude product, the crude product ethyl acetate and stone
The mixed solution recrystallization of oily ether, obtains 80.9 g white solids, yield 72.2%.
（2）67.2 g 3-（3- bromopyridine -2- base amino）Acrylonitrile（0.3 mol）, 62.2 g potassium carbonate（0.45
mol）, 0.67 g palladiums（6 mmol）And 0.67 g triethylenediamines（12 mmol）It is added to 500 mL N, N- dimethyl
In formamide, 20 h are reacted at 120 DEG C.Reaction is cooled to room temperature after terminating, remove solvent, adds 500 mL water and 500
ML ethyl acetate, the water layer separated merge organic phase with being extracted with ethyl acetate again afterwards twice, and extraction every time uses ethyl acetate
500 mL, first it is washed with water and uses saturated common salt water washing, anhydrous Na again2SO4Dry, evaporation solvent obtains 3- cyano-7-azaindoles
Crude product, 30.7 g white solid products, yield 71.6% are obtained with recrystallisation from isopropanol.
（3）100 mL methanol and 50 mL hydrochloric acid are added in reaction bulb（10 mol/L）, 28.6 g 3- cyano group -7-
Azaindole（0.2 mol）Dissolve wherein, the h of stirring reaction 15 at 70 DEG C.Reaction terminates to remove methanol, adds 100 mL
Water, pH=8 being neutralized to saturated sodium bicarbonate solution, there are a large amount of solids to generate, the suspension stands 3 h at 0 DEG C, filters,
Solid distillation water washing, is dried, the mixed solution of ethyl acetate and petroleum ether recrystallizes to obtain 27.7 g7- azaindole -3- first
Sour methyl esters, yield 78.6%.
Nmr analysis, elementary analysis, mass spectral analysis are carried out to final product, it is as a result as follows：
1H NMR (DMSO-d 6, 400 MHz) and δ：4.02 (s, 3H), 5.12 (s, 1H), 7.23 (t, 1H), 7.85
(s, 1H), 8.16-8.21 (m, 2H), 8.46 (d, 1H)；
Anal. Calcd for C9H8N2O2：C, 61.36；H, 4.58；N, 15.90；
ESI-MS m/z：177.1 [M+H]+。
Embodiment 2
（1）29.7 g sodium methoxides（0.55 mol）It is added in 1000 mL benzene, 22.6 g acetonitriles is added dropwise while stirring
（0.55 mol）With 40.7 g Ethyl formates（0.55 mol）Mixed solution, controlling reaction temperature be no more than 40 DEG C.Drip
Finish and continue to stir 2 h at room temperature.Then 86.5 g 2- amino -3- bromopyridines are sequentially added（0.5 mol）With 39.0 g acetic acid
（0.65 mol）, reactant mixture reacts 1 h at 40 DEG C.Reaction terminates to remove solvent, adds 800 mL water and 800 mL chlorine
Imitative, the water layer separated merges organic phase after being extracted twice with chloroform, and extraction every time uses the mL of chloroform 800, is washed with water, anhydrous
Sodium sulphate is dried, and evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Acrylonitrile crude product, the crude product ethyl acetate and stone
The mixed solution of oily ether recrystallizes to obtain 70.0 g white solids, yield 62.5%.
（2）67.2 g 3-（3- bromopyridine -2- base amino）Acrylonitrile（0.3 mol）, 45.1 g saleratus（0.45
mol）, 0.67 g palladiums（3 mmol）And 0.67 g triethylenediamines（6 mmol）It is added to 500 mLN- crassitudes
In ketone, 20 h are reacted at 120 DEG C.Reaction is cooled to room temperature after terminating, remove solvent, adds 500 mL water and 500 mL second
Acetoacetic ester, the water layer separated merge organic phase with being extracted with ethyl acetate again afterwards twice, and extraction every time uses ethyl acetate 500
ML, first it is washed with water and uses saturated common salt water washing, anhydrous Na again2SO4Dry, evaporation solvent obtains 3- cyano-7-azaindoles and slightly produced
Product, 24.4 g white solid products, yield 56.8% are obtained with recrystallisation from isopropanol.
（3）100 mL methanol and 50 mL hydrochloric acid are added in reaction bulb（12 mol/L）, 28.6 g 3- cyano group -7-
Azaindole（0.2 mol）Dissolving wherein, reacts 15 h at 70 DEG C.Reaction terminates to remove methanol, adds 100 mL water, uses
Saturated sodium bicarbonate solution is neutralized to pH=8, has a large amount of solids to generate, and the suspension stands 3 h at 0 DEG C, filters, and solid is used
Water washing is distilled, is dried, the mixed solution of ethyl acetate and petroleum ether recrystallizes to obtain 28.4 g7- azaindole -3- formic acid first
Ester, the % of yield 80.6.
Embodiment 3
（1）46.3 g potassium ethoxides（0.55 mol）It is added in 1000 mL toluene, 22.6 g acetonitriles is added dropwise while stirring
（0.55 mol）With 40.7 g Ethyl formates（0.55 mol）Mixed solution, controlling reaction temperature be no more than 20 DEG C, drip
Finish and continue to stir 3 h at room temperature, then sequentially add 86.5 g 2- amino -3- bromopyridines（0.5 mol）With 39.0 g acetic acid
（0.65 mol）, reactant mixture stirs 2.5 h at 30 DEG C.Reaction terminates to remove solvent, adds 800 mL water and 800 mL
Chloroform, the water layer separated merge organic phase after being extracted twice with chloroform, and extraction every time uses the mL of chloroform 800, is washed with water, nothing
Aqueous sodium persulfate is dried, and evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Acrylonitrile crude product, the crude product ethyl acetate and
The mixed solution of petroleum ether recrystallizes to obtain 85.7 g white solids, yield 76.5%
（2）67.2 g 3-（3- bromopyridine -2- base amino）Acrylonitrile（0.3 mol）, 36.9 g sodium acetates（0.45
mol）, 1.06 g palladium bichlorides（6 mmol）And 1.34 g triethylenediamines（12 mmol）It is added to 500 mL Isosorbide-5-Nitraes-dioxy six
In ring, 20 h are reacted at 100 DEG C.Reaction is cooled to room temperature after terminating, remove solvent, adds 500 mL water and 500 mL second
Acetoacetic ester, the water layer separated merge organic phase with being extracted with ethyl acetate again afterwards twice, and extraction every time uses ethyl acetate 500
ML, first it is washed with water and uses saturated common salt water washing, anhydrous Na again2SO4Dry, evaporation solvent obtains 3- cyano-7-azaindoles and slightly produced
Product, 26.8 g white solid products, yield 62.3% are obtained with recrystallisation from isopropanol.
（3）100 mL methanol and 100 mL hydrochloric acid are added in reaction bulb（10 mol/L）, 28.6 g 3- cyano group-
7- azaindoles（0.2 mol）Dissolving wherein, reacts 10 h at 80 DEG C.Reaction terminates to remove methanol, adds 100 mL water,
PH=8 are neutralized to saturated sodium bicarbonate solution, there are a large amount of solids to generate, the suspension stands 3 h at 0 DEG C, filters, solid
With distillation water washing, dry, the mixed solution of ethyl acetate and petroleum ether recrystallizes to obtain 30.8 g7- azaindole -3- formic acid first
Ester, yield 87.6%.
Embodiment 4
（1）46.3 g potassium ethoxides（0.55 mol）It is added in 1000 mL ethanol, 22.6 g acetonitriles is added dropwise while stirring
（0.55 mol）With 40.7 g Ethyl formates（0.55 mol）Mixed solution, controlling reaction temperature be no more than 10 DEG C, drip
Finish and continue to stir 5 h at room temperature.Then 86.5 g 2- amino -3- bromopyridines are sequentially added（0.5 mol）With 39.0 g acetic acid
（0.65 mol）, reactant mixture reacts 2 h at 30 DEG C.Reaction terminates to remove solvent, adds 800 mL water and 800 mL chlorine
Imitative, the water layer separated merges organic phase after being extracted twice with chloroform, and extraction every time uses the mL of chloroform 800, is washed with water, anhydrous
Sodium sulphate is dried, and evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Acrylonitrile crude product, the crude product ethyl acetate and stone
The mixed solution of oily ether recrystallizes to obtain 66.3 g white solids, yield 59.2%
（2）67.2 g 3-（3- bromopyridine -2- base amino）Acrylonitrile（0.3 mol）, 62.2 g potassium carbonate（0.45
mol）, 1.06 g palladiums（6 mmol）And 2.17 g dicyclohexylamine（12 mmol）It is added to 500 mL N, N- dimethyl second
In acid amides, 20 h are reacted at 120 DEG C.Reaction is cooled to room temperature after terminating, remove solvent, adds 500 mL water and 500 mL
Ethyl acetate, the water layer separated merge organic phase with being extracted with ethyl acetate again afterwards twice, and extraction every time uses ethyl acetate 500
ML, first it is washed with water and uses saturated common salt water washing, anhydrous Na again2SO4Dry, evaporation solvent obtains 3- cyano-7-azaindoles and slightly produced
Product, 29.2 g white solid products, yield 68.0% are obtained with recrystallisation from isopropanol.
（3）75 mL methanol and 100 mL hydrochloric acid are added in reaction bulb（8 mol/L）, 28.6 g 3- cyano group -7-
Azaindole（0.2 mol）Dissolving wherein, reacts 12 h at 80 DEG C.Reaction terminates to remove methanol, adds 100 mL water, uses
Saturated sodium bicarbonate solution is neutralized to pH=8, has a large amount of solids to generate, and the suspension stands 3 h at 0 DEG C, filters, and solid is used
Water washing is distilled, is dried, the mixed solution of ethyl acetate and petroleum ether recrystallizes to obtain 27.5 g7- azaindole -3- formic acid first
Ester, yield 78.2%.
Embodiment 5
（1）37.4 g caustic alcohols（0.55 mol）It is added in 1000 mL dimethylbenzene, 22.6 g second is added dropwise while stirring
Nitrile（0.55 mol）With 40.7 g Ethyl formates（0.55 mol）Mixed solution, controlling reaction temperature be no more than 20 DEG C.It is added dropwise
Finish and continue to stir 4 h at room temperature.Then 86.5 g 2- amino -3- bromopyridines are sequentially added（0.5 mol）With 39.0 g second
Acid（0.65 mol）.Reactant mixture reacts 3 h at 30 DEG C.Reaction terminates to remove solvent, adds 800 mL water and 800 mL
Chloroform, the water layer separated merge organic phase after being extracted twice with chloroform, and extraction every time uses the mL of chloroform 800, is washed with water, nothing
Aqueous sodium persulfate is dried, and evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Acrylonitrile crude product, the crude product ethyl acetate and
The mixed solution of petroleum ether recrystallizes to obtain 77.5 g white solids, yield 69.2%
（2）67.2 g 3-（3- bromopyridine -2- base amino）Acrylonitrile（0.3 mol）, 82.9 g potassium carbonate（0.6
mol）, 4.6 g cuprous iodides（30 mmol）And 6.7 g triethylenediamines（60 mmol）It is added in 500 mL ethanol,
Reacted at 100 DEG C after 20 h. reactions terminate and be cooled to room temperature, removed solvent, add 500 mL water and 500 mL acetic acid second
Ester, the water layer separated merge organic phase with being extracted with ethyl acetate again afterwards twice, and extraction every time use the mL of ethyl acetate 500, elder generation
It is washed with water and uses saturated common salt water washing, anhydrous Na again2SO4Dry, evaporation solvent obtains 3- cyano-7-azaindole crude products, uses
Recrystallisation from isopropanol obtains 22.0 g white solid products, yield 51.2%.
（3）75 mL methanol and 100 mL hydrochloric acid are added in reaction bulb（10 mol/L）, 28.6 g 3- cyano group -7-
Azaindole（0.2 mol）Dissolving wherein, reacts 10 h at 80 DEG C.Reaction terminates to remove methanol, adds 100 mL water, uses
Saturated sodium bicarbonate solution is neutralized to pH=8, has a large amount of solids to generate, and the suspension stands 3 h at 0 DEG C, filters, and solid is used
Water washing is distilled, is dried, the mixed solution of ethyl acetate and petroleum ether recrystallizes to obtain 28.4 g7- azaindole -3- formic acid first
Ester, yield 80.7%.
Embodiment 6
（1）54.0 g potassium isopropoxides（0.55 mol）It is added in 1000 mL toluene, 22.6 g second is added dropwise while stirring
Nitrile（0.55 mol）With 40.7 g Ethyl formates（0.55 mol）Mixed solution, controlling reaction temperature be no more than 30 DEG C, be added dropwise
Finish and continue to stir 3 h at room temperature.Then 86.5 g 2- amino -3- bromopyridines are sequentially added（0.5 mol）With 39.0 g second
Acid（0.65 mol）, reactant mixture reacts 1 h at 40 DEG C.Reaction terminates to remove solvent, adds 800 mL water and 800 mL
Chloroform, the water layer separated merge organic phase after being extracted twice with chloroform, and extraction every time uses the mL of chloroform 800, is washed with water, nothing
Aqueous sodium persulfate is dried, and evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Acrylonitrile crude product, the crude product ethyl acetate and
The mixed solution of petroleum ether recrystallizes to obtain 79.1 g white solids, yield 70.6%
（2）67.2 g 3-（3- bromopyridine -2- base amino）Acrylonitrile（0.3 mol）, 36.9 g sodium acetates（0.45
mol）, 4.6 g cuprous iodides（30 mmol）And 6.7 g triethylenediamines（60 mmol）It is added to 500 mLN, N- dimethyl
In acetamide, 20 h are reacted at 120 DEG C, reaction is cooled to room temperature after terminating, remove solvent.Add 500 mL water and 500
ML ethyl acetate, the water layer separated merge organic phase with being extracted with ethyl acetate again afterwards twice, and extraction every time uses ethyl acetate
500 mL, first it is washed with water and uses saturated common salt water washing, anhydrous Na again2SO4Dry, evaporation solvent obtains 3- cyano-7-azaindoles
Crude product, the crude product obtain 27.9 g white solid products, yield 64.9% with recrystallisation from isopropanol.
（3）100 mL methanol and 50 mL hydrochloric acid are added in reaction bulb（12 mol/L）, 28.6 g 3- cyano group -7-
Azaindole（0.2 mol）Dissolving wherein, reacts 20 h at 70 DEG C.Reaction terminates to remove methanol, adds 100 mL water, uses
Saturated sodium bicarbonate solution is neutralized to pH=8, has a large amount of solids to generate, and the suspension stands 3 h at 0 DEG C, filters, and solid is used
Water washing is distilled, is dried, the mixed solution of ethyl acetate and petroleum ether recrystallizes to obtain 29.0 g7- azaindole -3- formic acid first
Ester, yield 82.3%.
Claims (9)
- A kind of 1. synthetic method of 7- azaindoles -3- methyl formates, it is characterised in that：Comprise the following steps：（1）Highly basic is added in solvent orange 2 A, at 5 ~ 40 DEG C, the mixed solution of acetonitrile and Ethyl formate is added dropwise, is added dropwise 2 ~ 5 h of stirring obtain 3- hydroxy nitrile metal salts at room temperature afterwards；Then 2- amino -3- bromopyridines and acetic acid are sequentially added, instead Mixture is answered to stir 1 ~ 3 h at 20 ~ 40 DEG C；Reaction terminates to remove solvent orange 2 A, adds water and chloroform, the water layer separated use chlorine again Merge organic phase after imitative extraction, be washed with water, anhydrous sodium sulfate drying, evaporation solvent obtains 3-（3- bromopyridine -2- base amino）Third Alkene nitrile crude product, the crude product recrystallize to obtain white solid product with the mixed solution of ethyl acetate and petroleum ether；（2）3-（3- bromopyridine -2- base amino）Acrylonitrile, alkali and catalyst system and catalyzing are added in solvent B, at 80 ~ 120 DEG C 15 ~ 20 h are reacted, reaction end is cooled to room temperature, removes solvent B, adds water and ethyl acetate, the water layer separated use acetic acid again Merge organic phase after ethyl ester extraction, be first washed with water and use saturated common salt water washing again, anhydrous sodium sulfate drying, evaporation solvent obtains 3- Cyano-7-azaindole crude product, the crude product obtain white solid product with recrystallisation from isopropanol；The catalyst system and catalyzing is with two Cyclo-hexylamine is as the palladium chloride catalyst of part, using triethylenediamine as the palladium acetate catalyst of part, with Sanya second Base diamines is as the palladium chloride catalyst of part, using dicyclohexylamine as the palladium acetate catalyst of part, with triethylene two Amine is as one kind in the cuprous iodide catalyst of part；（3）3- cyano-7-azaindoles are added in the mixed liquor of hydrochloric acid and methanol, 10 ~ 20 h are reacted at 60 ~ 80 DEG C, Reaction terminates to add water, filters, and filtrate is neutralized with saturated sodium bicarbonate solution, has a large amount of solids to generate, and suspension is taken out after standing Filter, solid distillation water washing, 7- azaindole -3- first is recrystallized to obtain after drying with the mixed solution of ethyl acetate and petroleum ether Sour methyl esters.
- A kind of 2. synthetic method of 7- azaindoles -3- methyl formates according to claim 1, it is characterised in that：Step （1）Middle 2- amino -3- bromopyridines, acetonitrile, highly basic, the mol ratio of Ethyl formate and acetic acid are 1: 1.1: 1.1: 1.1: 1.3；2- ammonia The mass ratio of base -3- bromopyridines and solvent is 1:（9~12）；The volume ratio of ethyl acetate and petroleum ether is 1 in recrystallization solvent: 3。
- A kind of 3. synthetic method of 7- azaindoles -3- methyl formates according to claim 1 or 2, it is characterised in that：Step Suddenly（1）Described in highly basic be sodium methoxide, potassium methoxide, caustic alcohol, potassium ethoxide, sodium isopropylate, one kind in potassium isopropoxide；It is described molten Agent A is at least one of benzene,toluene,xylene, ethanol, isopropanol and tert-butyl alcohol.
- A kind of 4. synthetic method of 7- azaindoles -3- methyl formates according to claim 1, it is characterised in that：Step （2）Described in catalyst system and catalyzing be made up of catalyst and its part, the mol ratio of catalyst and its part is 1：（2~3）；The 3- （3- bromopyridine -2- base amino）Acrylonitrile, alkali, the mol ratio of catalyst are 1:（1~2）∶（0.001~0.1）；The 3-（3- bromines Pyridine -2- base amino）The mass ratio of acrylonitrile and solvent is 1:（10~12.5）.
- A kind of 5. synthetic method of 7- azaindoles -3- methyl formates according to claim 1 or 4, it is characterised in that：Step Suddenly（2）Described in alkali be potassium carbonate, saleratus, sodium acetate, triethylamine and pyridine in one kind.
- A kind of 6. synthetic method of 7- azaindoles -3- methyl formates according to claim 1 or 4, it is characterised in that：Step Suddenly（2）Described in solvent B be DMF, dimethyl sulfoxide (DMSO), 1-METHYLPYRROLIDONE, N, N- dimethylacetamides At least one of amine, toluene, Isosorbide-5-Nitrae-dioxane, acetonitrile and ethanol.
- A kind of 7. synthetic method of 7- azaindoles -3- methyl formates according to claim 1, it is characterised in that：Step （3）The mass ratio of middle 3- cyano-7-azaindoles, hydrochloric acid and methanol is 1:（2~4）∶（2~4）；Ethyl acetate in recrystallization solvent Volume ratio with petroleum ether is 1: 6.
- A kind of 8. synthetic method of 7- azaindoles -3- methyl formates according to claim 1 or 7, it is characterised in that：Step Suddenly（3）Described in hydrochloric acid concentration be 8 mol/L, 10 mol/L, one kind in 12 mol/L.
- A kind of 9. synthetic method of 7- azaindoles -3- methyl formates according to claim 1 or 7, it is characterised in that：Step Suddenly（3）Middle filtrate is neutralized to pH=8 with saturated sodium bicarbonate solution, has a large amount of solids to generate, and suspension stands 3 h at 0 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710024130.2A CN106588921B (en) | 2017-01-13 | 2017-01-13 | A kind of synthetic method of the methyl formate of 7 azaindole 3 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710024130.2A CN106588921B (en) | 2017-01-13 | 2017-01-13 | A kind of synthetic method of the methyl formate of 7 azaindole 3 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106588921A CN106588921A (en) | 2017-04-26 |
| CN106588921B true CN106588921B (en) | 2018-02-13 |
Family
ID=58586167
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710024130.2A Expired - Fee Related CN106588921B (en) | 2017-01-13 | 2017-01-13 | A kind of synthetic method of the methyl formate of 7 azaindole 3 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106588921B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320512A (en) * | 2018-10-26 | 2019-02-12 | 江苏理工学院 | A kind of synthetic method of azaindole substituted aryl Ethyl formate compound |
| CN110117252A (en) * | 2019-06-14 | 2019-08-13 | 南京博源医药科技有限公司 | A kind of preparation process of 2-aminopyridine -6- methyl formate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4319024A (en) * | 1979-03-29 | 1982-03-09 | Dynamit Nobel Aktiengesellschaft | Method of preparing β-alkoxyacrlonitriles |
| CN1594287A (en) * | 2004-07-16 | 2005-03-16 | 杭州科本化工有限公司 | Process for the preparation of 3-hydroxyacrylonitrile metal salts |
-
2017
- 2017-01-13 CN CN201710024130.2A patent/CN106588921B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4319024A (en) * | 1979-03-29 | 1982-03-09 | Dynamit Nobel Aktiengesellschaft | Method of preparing β-alkoxyacrlonitriles |
| CN1594287A (en) * | 2004-07-16 | 2005-03-16 | 杭州科本化工有限公司 | Process for the preparation of 3-hydroxyacrylonitrile metal salts |
Non-Patent Citations (2)
| Title |
|---|
| 7 -氮杂吲哚-3 -羧酸的合成工艺改进;蒋骏航;《药学实践杂志》;20070925;第25卷(第5期);312-314，345页 * |
| Preparation of 1,7-and 3,9-Dideazapurines from 2-Amino-3-iodo and 3-Amino-4-iodopyridines and Activated Acetylenes by Conjugate Addition and Copper-catalyzed Intramolecular Arylation;Ying Zhu 等;《The journal of organic chemistry》;20141021;第79卷(第22期);11270-11276 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106588921A (en) | 2017-04-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104945299B (en) | A kind of high-efficiency synthesis method of vildagliptin | |
| CN105884691B (en) | A kind of method for preparing Dexmedetomidine and its intermediate | |
| CN108129288B (en) | Synthesis method of trans-3-hydroxycyclobutylformic acid | |
| CN107235958A (en) | A kind of synthetic method for preparing PARP inhibitor Niraparib | |
| CN105294653B (en) | The preparation technology of Vonoprazan fumarate | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN106588921B (en) | A kind of synthetic method of the methyl formate of 7 azaindole 3 | |
| CN106946972A (en) | A kind of ursolic acid derivative with antitumor activity and preparation method thereof | |
| CN107235959A (en) | A kind of novel method for synthesizing for preparing cancer therapy drug Niraparib | |
| CN106938995A (en) | A kind of method of asymmetric synthesis of opthalmological bepotastine besilate | |
| CN114805327A (en) | Intermediate for thiohydantoin medicine and preparation method and application thereof | |
| CN101863954B (en) | Preparation method of N-tert-butyl-4-aza-5 alpha-androstane-3-ketone-17 beta-formamide | |
| CN113292479B (en) | Preparation method of 5-azaspiro [2.4] heptane and salt thereof | |
| CN106554354A (en) | The intermediate of Li Gelieting or its analog and Li Gelieting or the preparation method of its analog | |
| CN105693632A (en) | Preparation method of polysubstitution quinoxalin derivatives | |
| CN107417606B (en) | Method for converting N-cyanomethyl bis (trifluoromethyl) nicotinamide into flonicamid and application | |
| CN107176906A (en) | A kind of synthetic method of substitution indone | |
| CN109879805B (en) | Preparation method of apatinib | |
| CN102206182B (en) | Method for synthesizing Rimonabant hydrochloride | |
| CN112939893A (en) | Synthesis method of 4- (4-aminophenyl) -3-morpholinone | |
| CN108409648A (en) | A kind of preparation method of Sorafenib Tosylate correlation intermediate | |
| CN109988098A (en) | The synthetic method of one kind (R)-N- tertbutyloxycarbonyl -3- hydroxymethyl piperidine | |
| CN104163798A (en) | Synthesis method of 3-amino-8-trifluoromethyl quinoline | |
| CN104003944B (en) | A kind of preparation method of mepanipyrim | |
| CN109134395A (en) | The synthetic method of Parecoxib Sodium Isomeric impurities |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180213 |