CN104496913A - Method for preparing 5-substituted-2,4-dimethylsulfenyl pyrimidine - Google Patents
Method for preparing 5-substituted-2,4-dimethylsulfenyl pyrimidine Download PDFInfo
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- CN104496913A CN104496913A CN201410800373.7A CN201410800373A CN104496913A CN 104496913 A CN104496913 A CN 104496913A CN 201410800373 A CN201410800373 A CN 201410800373A CN 104496913 A CN104496913 A CN 104496913A
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- Prior art keywords
- pyrimidines
- dimethyl sulphur
- pyrimidine
- sulphur
- dimethyl
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- 238000000034 method Methods 0.000 title claims abstract description 17
- -1 5-substituted-2,4-dimethylsulfenyl pyrimidine Chemical class 0.000 title abstract description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 12
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- BNOODXBBXFZASF-UHFFFAOYSA-N [Na].[S] Chemical compound [Na].[S] BNOODXBBXFZASF-UHFFFAOYSA-N 0.000 claims abstract description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Substances [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000004327 boric acid Substances 0.000 claims abstract description 6
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 239000005864 Sulphur Substances 0.000 claims description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 150000003230 pyrimidines Chemical class 0.000 claims description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- FREJAOSUHFGDBW-UHFFFAOYSA-N pyrimidine-5-carbaldehyde Chemical compound O=CC1=CN=CN=C1 FREJAOSUHFGDBW-UHFFFAOYSA-N 0.000 claims description 5
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 4
- 235000011089 carbon dioxide Nutrition 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 4
- 239000007787 solid Substances 0.000 abstract description 4
- 239000000575 pesticide Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- NXOAMBKQNWXFAM-UHFFFAOYSA-N 2,4-bis(methylsulfanyl)pyrimidine-5-carbaldehyde Chemical compound CSC1=NC=C(C=O)C(SC)=N1 NXOAMBKQNWXFAM-UHFFFAOYSA-N 0.000 abstract 1
- ODSORSOVOMCEHN-UHFFFAOYSA-N 2,4-bis(methylsulfanyl)pyrimidine-5-carboxylic acid Chemical compound CSC1=NC=C(C(O)=O)C(SC)=N1 ODSORSOVOMCEHN-UHFFFAOYSA-N 0.000 abstract 1
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/58—Two sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses a method for preparing 5-substituted-2,4-dimethylsulfenyl pyrimidine, relates to a synthesis method of an important medicine and pesticide midbody, and belongs to the technical field of organic chemical synthesis. The method is characterized by comprising the following steps: I, by taking 5-bromine-2,4-dichloropyrimidine as an initial raw material, implementing reaction with sulfur sodium methylate at the room temperature so as to generate 5-bromin-2,4-dimethyl sulfenyl pyrimidine; II, in the presence of nitrogen, implementing reaction on 5-bromin-2,4-dimethyl sulfenyl pyrimidine with butyl lithium at low temperature, further implementing reaction with trimethyl borate ester, N,N-dimethylformamide and solid carbon dioxide so as to generate 2,4-dimethyl sulfenyl pyrimidine-5-boric acid, 2,4-dimethyl sulfenyl pyrimidine-5-formaldehyde and 2,4-dimethyl sulfenyl pyrimidine-5-formic acid. The method has the beneficial effects that a generated target compound is high in yield, good in purity, wide in application prospect, simple and convenient to operate, easily available in raw materials, good in reaction selectivity and environment-friendly, the production is easy to amplify, and industrial products can be produced.
Description
Technical field
The present invention relates to the synthetic method relating to the important medicine of a class and pesticide intermediate, belong to organic chemical synthesis technical field, refer to that one prepares the method for 5-replacement-2,4-dimethyl sulphur-based pyrimidines especially.
Background technology
5-replaces-2,4-dimethyl sulphur-based pyrimidine is because containing two methylthio group groups, the important medicine of a class and pesticide intermediate, their synthetic method seldom reported by existing document, and the present invention uses the weak nucleophilic reagent sulphur sodium methylate of two equivalents and bromo-2, the 4-dichloro pyrimidines of 5-to react 2, introduce two methylthio groups for 4, and then with butyllithium effect, then add other electrophilic reagents generate 5-replace-2,4-dimethyl sulphur-based pyrimidine organic compound.This organic micromolecule is the important intermediate of some medicines of synthesis and agricultural chemicals, also can be used as organic chemical industry's reagent.Therefore, this kind of 5-replacement-2,4-dimethyl sulphur-based pyrimidines are with a wide range of applications.
Summary of the invention
The present invention compensate for the shortcoming in the preparation of some 5-replacement-2,4-dimethyl sulphur-based pyrimidines, and provide a class 5-and replace the phonetic preparation method of-2,4-dimethyl sulphur-baseds, good product purity, its stable in properties, easily realizes commercially produced product, and its syntheti c route is as follows:
One, the preparation of bromo-2, the 4-dimethyl sulphur-based pyrimidines of 5-: by with bromo-2, the 4-dichloro pyrimidines of 5-for starting raw material, at room temperature react with sulphur sodium methylate, generate 5-bromo-2,4-dimethyl sulphur-based pyrimidines.
Two, bromo-2, the 4-dimethyl sulphur-based pyrimidines of 5-under nitrogen protection, reacts in low temperature and butyllithium; again respectively with trimethyl borate, DMF and solidified carbon dioxide reaction; regulate PH=3-4 with dilute hydrochloric acid, with organic solvent extraction, be separated; or filter, dry, concentrated solvent; purifying obtains 2,4-dimethyl sulphur-based pyrimidine-5-boric acid, and 2; 4-dimethyl sulphur-based pyrimidine-5-formaldehyde and 2,4-dimethyl sulphur-based pyrimidine-5-formic acid.
In described step one and step 2, reaction solvent is tetrahydrofuran (THF).
In described step one, the mol ratio of bromo-2, the 4-dichloro pyrimidines of raw material 5-and sulphur sodium methylate is 1:2.
In described step 2, low temperature is-78 DEG C.
In described step 2, organic extraction solvent is ether or ethyl acetate.
In described step 2, diluted acid is 1N hydrochloric acid.
In described step 2, purification technique is recrystallization.
In described step 2, raw material 5-bromo-2, the mol ratio of 4-dimethyl sulphur-based pyrimidine and butyllithium and trimethyl borate is 1:1.1:1.05,5-bromo-2,4-dimethyl sulphur-based pyrimidine and butyllithium and N, the mol ratio of N-dimethylformamide is the mol ratio of bromo-2, the 4-dimethyl sulphur-based pyrimidines of 1:1.1:1.05,5-and butyllithium and carbonic acid gas is 1:1.1:40.
Embodiment
Be clearly and completely described below in conjunction with the technical scheme in the embodiment of the present invention, obviously, described embodiment is only some embodiments of the present invention, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
Embodiment 1
The preparation of bromo-2, the 4-dimethyl sulphur-based pyrimidines of 5-:
In 5L reaction flask, add bromo-2, the 4-dichloro pyrimidines (1.31mol) of 300g 5-and 2L tetrahydrofuran (THF), be chilled to 0 DEG C, slowly add 184.55g sulphur sodium methylate (2.63mol), slowly rise to room temperature, react after 12 hours, to go out reaction with shrend, be separated organic phase, add extraction into ethyl acetate aqueous phase, merge organic phase, washing, salt is washed, dry, concentrated solvent, the thick product normal hexane recrystallization obtained, generate bromo-2, the 4-dimethyl sulphur-based pyrimidine 280g of solid 5-, productive rate 75%, GC>98%, 1HNMR (CDCl
3)): 2.46ppm, unimodal (6H); 8.21ppm, unimodal (1H).
Embodiment 2
The preparation of 2,4-dimethyl sulphur-based pyrimidine-5-boric acid:
In 3L reaction flask, add 100g 5-bromo-2, 4-dimethyl sulphur-based pyrimidine (0.4mol) and 1L tetrahydrofuran (THF), be chilled to-78 DEG C, slow dropping 168mL butyllithium (0.44mol, 2.6N in hexanes), reaction system was-78 DEG C of reactions 2 hours, drip 78.63g trimethyl borate (0.42mol),-78 DEG C of reactions 1 hour, slowly rise to room temperature, this process need 9 hours, drip the dilute hydrochloric acid of 1N, regulate PH=3-4, be separated organic phase, add extracted with diethyl ether aqueous phase, merge organic phase, washing, salt is washed, dry, concentrated solvent, the thick product normal hexane recrystallization obtained, generate 2, 4-dimethyl sulphur-based pyrimidine-5-boric acid 63g, productive rate 73%, GC>98%, 1HNMR ((DMSO-d
6/ D
2o): 2.21ppm, unimodal (3H), 2.26ppm, unimodal (3H), 8.21ppm, unimodal (1H).
Embodiment 3
The preparation of 2,4-dimethyl sulphur-based pyrimidine-5-formaldehyde:
In 3L reaction flask, add 100g 5-bromo-2, 4-dimethyl sulphur-based pyrimidine (0.4mol) and 1L tetrahydrofuran (THF), be chilled to-78 DEG C, slow dropping 168mL butyllithium (0.44mol, 2.6N in hexanes), reaction system was-78 DEG C of reactions 2 hours, drip 30.70g N, N-dimethylformamide (0.42mol),-78 DEG C of reactions 1 hour, slowly rise to room temperature, this process need 9 hours, drip the dilute hydrochloric acid of 1N, regulate PH=3-4, be separated organic phase, add extracted with diethyl ether aqueous phase, merge organic phase, washing, salt is washed, dry, concentrated solvent, the thick product normal hexane recrystallization obtained, generate 2, 4-dimethyl sulphur-based pyrimidine-5-formaldehyde 59.4g, productive rate 74%, GC>98%, HNMR (CDCl
3)): 2.41ppm, unimodal (3H), 2.46ppm, unimodal (3H), 8.41ppm, unimodal (1H), 9.96ppm, unimodal (1H).13CNMR(CDCl
3))：12.92ppm,14.55ppm,121.97ppm,160.19ppm,171.84ppm,175.82ppm,188.26ppm。
Embodiment 4
The preparation of 2,4-dimethyl sulphur-based pyrimidine-5-formic acid:
In 3L reaction flask, add 60g 5-bromo-2, 4-dimethyl sulphur-based pyrimidine (0.24mol) and 1L tetrahydrofuran (THF), be chilled to-78 DEG C, slow dropping 102mL butyllithium (0.26mol, 2.6N in hexanes), reaction system was-78 DEG C of reactions 2 hours, add the carbonic acid gas (9.6mol) of 422g solid,-78 DEG C of reactions 1 hour, slowly rise to room temperature, this process need 9 hours, drip the dilute hydrochloric acid of 1N, regulate PH=3-4, be separated organic phase, add extraction into ethyl acetate aqueous phase, merge organic phase, washing, salt is washed, dry, concentrated solvent, the thick product normal hexane rinsing obtained, generate solid 2, 4-dimethyl sulphur-based pyrimidine-5-formic acid 48.8g, productive rate 94%, GC>98%, 1HNMR ((DMSO-d
6/ D
2o): 2.21ppm, unimodal (3H), 2.47ppm, unimodal (3H), 8.82ppm, unimodal (1H).
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (9)
1. the method prepared 5-and replace-2,4-dimethyl sulphur-based pyrimidines, comprises the preparation of bromo-2, the 4-dimethyl sulphur-based pyrimidines of 5-, the preparation of 2,4-dimethyl sulphur-based pyrimidine-5-boric acid, 2, the preparation of 4-dimethyl sulphur-based pyrimidine-5-formaldehyde and the preparation of 2,4-dimethyl sulphur-based pyrimidine-5-formic acid, is characterized in that:
1. the structure of 5-replacement-2,4-dimethyl sulphur-based pyrimidines is as follows:
2. by with bromo-2, the 4-dichloro pyrimidines of 5-for starting raw material, at room temperature react with sulphur sodium methylate, generation 5-bromo-2,4-dimethyl sulphur-based pyrimidines;
3. bromo-2, the 4-dimethyl sulphur-based pyrimidines of 5-under nitrogen protection, with butyllithium effect under low temperature; again respectively with trimethyl borate, DMF; with solidified carbon dioxide reaction, regulate PH=3-4 with dilute hydrochloric acid, with organic solvent extraction; be separated, or filter, dry; concentrated solvent, purifying obtains 2,4-dimethyl sulphur-based pyrimidine-5-boric acid; 2,4-dimethyl sulphur-based pyrimidine-5-formaldehyde and 2,4-dimethyl sulphur-based pyrimidine-5-formic acid.
2. 5-as claimed in claim 1 replaces the preparation method of-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 2. in reaction solvent be tetrahydrofuran (THF).
3. one according to claim 1 is prepared 5-and is replaced the method for-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 2. in, the mol ratio of bromo-2, the 4-dichloro pyrimidines of raw material 5-and sulphur sodium methylate is 1:2.
4. one according to claim 1 is prepared 5-and is replaced the method for-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 3. in, reaction solvent is tetrahydrofuran (THF).
5. one according to claim 1 is prepared 5-and is replaced the method for-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 3. in, low temperature is-78 DEG C.
6. one according to claim 1 is prepared 5-and is replaced the method for-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 3. in, organic extraction solvent is ether or ethyl acetate.
7. one according to claim 1 is prepared 5-and is replaced the method for-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 3. in, purification technique is recrystallization.
8. one according to claim 1 is prepared 5-and is replaced-2, the method of 4-dimethyl sulphur-based pyrimidine, it is characterized in that: described 3. in, the mol ratio of bromo-2, the 4-dimethyl sulphur-based pyrimidines of raw material 5-and butyllithium and trimethyl borate is 1:1.1:1.05,5-bromo-2,4-dimethyl sulphur-based pyrimidine and butyllithium and N, the mol ratio of N-dimethylformamide is the mol ratio of bromo-2, the 4-dimethyl sulphur-based pyrimidines of 1:1.1:1.05,5-and butyllithium and carbonic acid gas is 1:1.1:40.
9. one according to claim 1 is prepared 5-and is replaced the method for-2,4-dimethyl sulphur-based pyrimidines, it is characterized in that: described 3. in, diluted acid is 1N hydrochloric acid.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410800373.7A CN104496913B (en) | 2014-12-22 | 2014-12-22 | A method of preparing 5- substitution -2,4- dimethyl sulphur-based pyrimidines |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410800373.7A CN104496913B (en) | 2014-12-22 | 2014-12-22 | A method of preparing 5- substitution -2,4- dimethyl sulphur-based pyrimidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104496913A true CN104496913A (en) | 2015-04-08 |
| CN104496913B CN104496913B (en) | 2018-08-21 |
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| CN201410800373.7A Expired - Fee Related CN104496913B (en) | 2014-12-22 | 2014-12-22 | A method of preparing 5- substitution -2,4- dimethyl sulphur-based pyrimidines |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693707A (en) * | 2016-04-05 | 2016-06-22 | 叶芳 | 4-bissulfurylamidino substituted pyrimidine compounds and preparation method thereof |
| CN109694354A (en) * | 2019-02-25 | 2019-04-30 | 南京哈柏医药科技有限公司 | The synthetic method of the chloro- 2- methylthiopyrimidine -5- Ethyl formate of 4- |
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|---|---|---|---|---|
| CN1333751A (en) * | 1998-12-23 | 2002-01-30 | 辛根塔参与股份公司 | Substituted pyridine Herbicides |
| CN1803880A (en) * | 2005-12-09 | 2006-07-19 | 武汉大学 | Non-linear optical polyurethane high molecule containing chromophore lateral group |
-
2014
- 2014-12-22 CN CN201410800373.7A patent/CN104496913B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1333751A (en) * | 1998-12-23 | 2002-01-30 | 辛根塔参与股份公司 | Substituted pyridine Herbicides |
| CN1803880A (en) * | 2005-12-09 | 2006-07-19 | 武汉大学 | Non-linear optical polyurethane high molecule containing chromophore lateral group |
Non-Patent Citations (3)
| Title |
|---|
| FABRICE COTTET ET AL.: "Further metalations and functionalizations of chloro-, bromo- and iodo(trifluoromethyl)pyridines", 《SYNTHESIS》 * |
| LUCJAN STREKOWSKI ET AL.: "Facile Preparation of 6-Substituted Uracils", 《SYNTHESIS》 * |
| LUCJAN STREKOWSKI ET AL.: "The Cine-Substitution Reaction of 5-Bromopyrimidines by Lithium Reagents", 《J. ORG. CHEM.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693707A (en) * | 2016-04-05 | 2016-06-22 | 叶芳 | 4-bissulfurylamidino substituted pyrimidine compounds and preparation method thereof |
| CN109694354A (en) * | 2019-02-25 | 2019-04-30 | 南京哈柏医药科技有限公司 | The synthetic method of the chloro- 2- methylthiopyrimidine -5- Ethyl formate of 4- |
| CN109694354B (en) * | 2019-02-25 | 2023-10-24 | 南京哈柏医药科技有限公司 | Synthesis method of 4-chloro-2-methylthiopyrimidine-5-ethyl formate |
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| CN104496913B (en) | 2018-08-21 |
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Granted publication date: 20180821 Termination date: 20211222 |