CN107011256A - A kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2 - Google Patents
A kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2 Download PDFInfo
- Publication number
- CN107011256A CN107011256A CN201710433506.5A CN201710433506A CN107011256A CN 107011256 A CN107011256 A CN 107011256A CN 201710433506 A CN201710433506 A CN 201710433506A CN 107011256 A CN107011256 A CN 107011256A
- Authority
- CN
- China
- Prior art keywords
- amino
- methoxyl
- reaction
- iodo
- iodosuccinimides
- 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.)
- Withdrawn
Links
- 238000010189 synthetic method Methods 0.000 title claims abstract description 10
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000003927 aminopyridines Chemical class 0.000 title abstract 3
- -1 methoxyl group Chemical group 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 230000026045 iodination Effects 0.000 claims abstract description 4
- 238000006192 iodination reaction Methods 0.000 claims abstract description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical class IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000000463 material Substances 0.000 claims abstract description 3
- 238000012805 post-processing Methods 0.000 claims abstract description 3
- 238000000746 purification Methods 0.000 claims abstract description 3
- 230000000977 initiatory effect Effects 0.000 claims abstract 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- QPHBCOSULYSASF-UHFFFAOYSA-N 4-methoxypyridin-2-amine Chemical class COC1=CC=NC(N)=C1 QPHBCOSULYSASF-UHFFFAOYSA-N 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 229960001866 silicon dioxide Drugs 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims 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 1
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000007445 Chromatographic isolation Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- QEQGAEHEPGMNCC-UHFFFAOYSA-N fluoromethanesulfonic acid;silver Chemical compound [Ag].OS(=O)(=O)CF QEQGAEHEPGMNCC-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The present invention provides a kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2, using the methoxypyridine of 2 amino 4 as initiation material, reacted, reacted after terminating through post-processing, obtaining the aminopyridine of 5 iodine, 4 methoxyl group 2 after purification as iodination reagent using N N-iodosuccinimides.Compared to the prior art, reaction condition is gentle by the present invention, and synthetic route is simple, and the reaction time is short, and cost is low.
Description
Technical field
The present invention relates to a kind of synthetic method of the iodo- 4- methoxyl groups-PAs of 5-.
Background technology
The iodo- 4- methoxyl groups-PAs of 5- are used widely as medicine intermediate., Phillip in 2013
P.Sharp etc. is reported using 2- amino-4-methoxyls pyridine as raw material on Organic Letters magazines first, and iodine, three
Fluoromethane sulfonic acid silver reaction, utilizes the synthetic method of microwave technology.But this method needs microwave reaction device, and exist anti-
Answer temperature high, reaction time length, it is necessary to reagent costly and the shortcomings of the amount of reagent that needs is big.
So far, on the not disclosed report of synthetic method by the use of N- N-iodosuccinimides as iodination reagent.
The content of the invention
It is an object of the invention to provide a kind of synthetic method of the iodo- 4- methoxyl groups-PAs of 5-, to simplify its synthesis
Technique, and reduce production cost.
The present invention is achieved through the following technical solutions：
A kind of synthetic method of the iodo- 4- methoxyl groups-PAs of 5-, it is former by starting of 2- amino-4-methoxyls pyridine
Material, is reacted using N- N-iodosuccinimides as iodination reagent, is reacted after terminating through post-processing, obtaining after purification described
The iodo- 4- methoxyl groups-PAs of 5-.
Further, the synthetic method of the iodo- 4- methoxyl groups-PAs of the 5-, comprises the following steps：0-50℃
Under, 2- amino-4-methoxyl pyridines react in polar solvent with N- N-iodosuccinimides, and reaction is diluted with water after terminating,
Crude product is filtrated to get, after chromatography, the iodo- 4- methoxyl groups-PAs of the 5- are obtained.
The synthetic line of the present invention is as follows：
It is preferred that, the polar solvent is DMF.
Above-mentioned preferred 20-30 DEG C of reaction temperature, preferably 25 DEG C.
2- amino-4-methoxyl pyridines are in N,N-dimethylformamide and the N- N-iodosuccinimide reaction time is
30-90 minutes, preferred reaction time was 50-70 minutes, preferably 60 minutes.
The chromatographic column is preferred to use silica gel chromatographic column.
The beneficial effects of the invention are as follows：Compared to the prior art, reaction condition of the present invention is gentle, and synthetic route is simple, instead
Short between seasonable, cost is low.
Embodiment
Present pre-ferred embodiments are given below, to describe technical scheme in detail.According to following explanation and power
Sharp claim, advantages and features of the invention will become apparent from.
Embodiment 1
2- amino-4-methoxyls pyridine (7.8g, 62.9mmol), DMF are added into three-necked flask
(150mL)；N- N-iodosuccinimides (14.1g, 62.7mmol) are added at 25 DEG C.25 DEG C of reaction solution is stirred 60 minutes.Reaction
Liquid is diluted with water (400mL), is filtrated to get solid crude product, (dichloromethane is separated by silica gel column chromatography：Methanol=20:1),
Obtain brown solid, i.e. target product 5- iodo- 4- methoxyl groups-PA (7.24g, 28.9mmol, 46%).It is common through nuclear-magnetism
Measurement result of shaking is as follows：1H NMR(400MHz,CDCl3):8.16(s,1H),5.98(s,1H),4.44(br,2H),3.86(s,
3H) ppm. liquid chromatograph mass spectrographies testing result is as follows：LC-MS(ESI):m/z 250.90[M+H]+。
Embodiment 2
Step 1：2- amino-4-methoxyl pyridines are in N,N-dimethylformamide and when N- N-iodosuccinimides react
Between be 30 minutes, reaction temperature be 50 DEG C, reaction solution with water (400mL) dilute, solid crude product is filtrated to get, by silicagel column
Chromatographic isolation (dichloromethane：Methanol=20:1) the iodo- 4- methoxyl groups-PA of brown solid, i.e. target product 5-, is obtained
(yield 45.2%).It is as follows through nuclear magnetic resonance measuring result：1H NMR(400MHz,CDCl3):8.16(s,1H),5.98(s,
1H), 4.44 (br, 2H), 3.86 (s, 3H) ppm. liquid chromatograph mass spectrography testing results are as follows：LC-MS(ESI):m/z
250.90[M+H]+。
Embodiment 3
Step 1：2- amino-4-methoxyl pyridines are in N,N-dimethylformamide and when N- N-iodosuccinimides react
Between be 90 minutes, reaction temperature be 0 DEG C, reaction solution with water (400mL) dilute, solid crude product is filtrated to get, by silicagel column
Chromatographic isolation (dichloromethane：Methanol=20:1) the iodo- 4- methoxyl groups-PA of brown solid, i.e. target product 5-, is obtained
(yield 45.5%).It is as follows through nuclear magnetic resonance measuring result：1H NMR(400MHz,CDCl3):8.16(s,1H),5.98(s,
1H), 4.44 (br, 2H), 3.86 (s, 3H) ppm. liquid chromatograph mass spectrography testing results are as follows：LC-MS(ESI):m/z
250.90[M+H]+。
Foregoing description is only the description to present pre-ferred embodiments, not to any restriction of the scope of the invention, this hair
Any change, modification that the those of ordinary skill in bright field does according to the disclosure above content, belong to the protection of claims
Scope.
Claims (9)
1. a kind of synthetic method of the iodo- 4- methoxyl groups-PAs of 5-, it is characterised in that with 2- amino-4-methoxyl pyridines
For initiation material, reacted using N- N-iodosuccinimides as iodination reagent, reaction terminate after through post processing, after purification
Obtain the iodo- 4- methoxyl groups-PAs of the 5-.
2. the method as described in claim 1, it is characterised in that comprise the following steps：At 0-50 DEG C, 2- amino-4-methoxyls
Pyridine reacts in polar solvent with N- N-iodosuccinimides, and reaction is diluted with water after terminating, and is filtrated to get crude product, passes through
After chromatography, the iodo- 4- methoxyl groups-PAs of the 5- are obtained.
3. method as claimed in claim 2, it is characterised in that the polar solvent is DMF.
4. the method as described in claim 1, it is characterised in that 2- amino-4-methoxyl pyridines are in DMF
It is 20-30 DEG C to neutralize N- N-iodosuccinimides reaction temperature.
5. the method as described in claim 1, it is characterised in that the reaction temperature is 25 DEG C.
6. the method as described in claim 1, it is characterised in that 2- amino-4-methoxyl pyridines are in DMF
It is 30-90 minutes to neutralize the N- N-iodosuccinimide reaction time.
7. the method as described in claim 1, it is characterised in that the reaction time is 50-70 minutes.
8. the method as described in claim 1, it is characterised in that the reaction time is 60 minutes.
9. the method as described in claim 1, it is characterised in that the chromatographic column is silicagel column.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710433506.5A CN107011256A (en) | 2017-06-09 | 2017-06-09 | A kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710433506.5A CN107011256A (en) | 2017-06-09 | 2017-06-09 | A kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107011256A true CN107011256A (en) | 2017-08-04 |
Family
ID=59452727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710433506.5A Withdrawn CN107011256A (en) | 2017-06-09 | 2017-06-09 | A kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107011256A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232562A (en) * | 2018-10-24 | 2019-01-18 | 康化（上海）新药研发有限公司 | A kind of synthetic method of the chloro- 6- carboxylic acid of 7- azaindole -5- |
| CN116874416A (en) * | 2023-01-16 | 2023-10-13 | 南京合巨药业有限公司 | Preparation method of 4-iodo-3-methoxypyridine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120015926A1 (en) * | 2008-11-10 | 2012-01-19 | Ling Tong | Compounds for the treatment of inflammatory disorders |
-
2017
- 2017-06-09 CN CN201710433506.5A patent/CN107011256A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120015926A1 (en) * | 2008-11-10 | 2012-01-19 | Ling Tong | Compounds for the treatment of inflammatory disorders |
Non-Patent Citations (1)
| Title |
|---|
| PIERRE L. BEAULIEU，ET AL: "Aza follow-ups to BI207524, a thumb pocket 1 HCV NS5B polymerase inhibitor. Part1: Mitigating the genotoxic liability of an aniline metabolite", 《BIOORGANIC MEDICINAL CHEMISTRY LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232562A (en) * | 2018-10-24 | 2019-01-18 | 康化（上海）新药研发有限公司 | A kind of synthetic method of the chloro- 6- carboxylic acid of 7- azaindole -5- |
| CN116874416A (en) * | 2023-01-16 | 2023-10-13 | 南京合巨药业有限公司 | Preparation method of 4-iodo-3-methoxypyridine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yuan et al. | Dynamic pH junction high-speed counter-current chromatography coupled with microwave-assisted extraction for online separation and purification of alkaloids from Stephania cepharantha | |
| CN107011256A (en) | A kind of synthetic method of the aminopyridine of 5 iodine, 4 methoxyl group 2 | |
| CN104370724B (en) | A kind of fluorenone derivatives and preparation method thereof, and the oxide-reduction method of synthesis Fluorenone | |
| CN112376076B (en) | Preparation method of azoxybenzene | |
| CN110669002B (en) | Synthetic method of 2-fluoro-3-hydroxypyridine-4-carboxylic acid | |
| CN107880063B (en) | Method for synthesizing subprostrate sophora | |
| CN104387331A (en) | Preparation method of pyrazine derivative | |
| CN103319411A (en) | Preparation method of imidafenacin | |
| CN105348094B (en) | A kind of acyl chlorides and the addition product of alkynes and preparation method thereof | |
| CN104177293A (en) | Synthesis method of 5-amino-7-trifluoromethyl quinoline and 5-trifluoromethyl-7-amino quinoline | |
| CN111138269B (en) | Process method for preparing 2-butanone acid sodium salt | |
| CN110272332A (en) | A kind of carbon nano ring and its synthetic method of methoxyl group modification | |
| CN102241634B (en) | Preparation method of 2-nitro-4,5-dicyan-1H-imidazole | |
| CN105541684B (en) | A kind of oxide-reduction method of four acetylene compounds and Diphenylthiocarbazone | |
| CN105330613A (en) | Oxathiadiazole-2-oxide compound and preparation method thereof | |
| CN105001231A (en) | A kind of preparation method of ginkgolide K | |
| CN107021954A (en) | A kind of fumaric acid Lu handkerchief is for fragrant new impurity and preparation method thereof and detection method | |
| JP6435505B2 (en) | Compound | |
| CN105001074A (en) | Method for preparing 2,3-dibromo-succinic acid | |
| CN106045995A (en) | Synthesizing method of 5-bromine-1H-pyrrolo[2,3-b]pyridine | |
| Kamano et al. | Steroids and related natural products. 93. Bufadienolides. 30. Synthesis of the Ch'an Su component 15. beta.-hydroxybufalin | |
| CN105130841A (en) | Preparation method of 3-iodophenyl azide compound | |
| SU421183A3 (en) | METHOD OF OBTAINING STEROIDS, NON-ASSISTED IN POSITION 9 | |
| CN104356139B (en) | Synthetic method of nitidine chloride | |
| Raposo et al. | Microwave-assisted protocols applied to the synthesis of 1′, 2, 3, 3′, 4, 4′-hexa-O-benzylsucrose |
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 | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20170804 |