CN103880846A - Preparation method of triazolopyrimidine sulfydryl type compound - Google Patents

Preparation method of triazolopyrimidine sulfydryl type compound Download PDF

Info

Publication number
CN103880846A
CN103880846A CN201410089040.8A CN201410089040A CN103880846A CN 103880846 A CN103880846 A CN 103880846A CN 201410089040 A CN201410089040 A CN 201410089040A CN 103880846 A CN103880846 A CN 103880846A
Authority
CN
China
Prior art keywords
compound
alkyl
formula
preparation
iii
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.)
Granted
Application number
CN201410089040.8A
Other languages
Chinese (zh)
Other versions
CN103880846B (en
Inventor
胡俊铎
赖玉龙
刘维
郭群震
虞小华
蔡国平
陈邦池
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Oriental Luzhou Agrochemicals Co Ltd
Original Assignee
Oriental Luzhou Agrochemicals Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Oriental Luzhou Agrochemicals Co Ltd filed Critical Oriental Luzhou Agrochemicals Co Ltd
Priority to CN201410089040.8A priority Critical patent/CN103880846B/en
Publication of CN103880846A publication Critical patent/CN103880846A/en
Priority to PCT/CN2015/073741 priority patent/WO2015135439A1/en
Application granted granted Critical
Publication of CN103880846B publication Critical patent/CN103880846B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a preparation method of a triazolopyrimidine sulfydryl type compound. The method comprises the following steps: rearranging and substituting the compound as shown in formula (II) under alcohol-alkali action to obtain the triazolopyrimidine sulfydryl type compound as show in formula (I). The method disclosed by the invention expands a way and a material resource of the existing preparation method, does not produce environment-unfriendly byproducts and has an industrial application value.

Description

A kind of preparation method of triazolo pyrimidine sulfydryl type compound
Technical field
The present invention relates to the synthetic of organic heterocyclic molecule, the especially preparation method of triazolo pyrimidine sulfhydryl compound.
Technical background
Triazolo pyrimidine sulfhydryl compound (I) is the important intermediate of preparing triazolopyrimidine sulfonamides herbicide.
US6162915 and US5488109 disclose a kind of method of preparing triazolo pyrimidine sulfhydryl compound.For example, formula IV compound is reacted with sodium ethylate and prepare compound (V).
Figure BDA0000475822770000012
Although the method transformation efficiency is higher, in reaction, supervene the thiomethyl alcohol (VI) of a large amount of foul smelling tastes, there is serious environmental issue.
Summary of the invention
The present invention, through deep research, finds compound and alcohol alkali reaction shown in formula II, can prepare the compound shown in formula I.Because the method not only can be reset the sulfydryl in the triazole ring in formula II, methoxyl group on all right substituted pyrimidines ring, thereby can be wider widen approach and the raw material sources of preparing triazolo pyrimidine sulfydryl type compound, the raw materials cost of preparing the former medicine of triazolopyrimidine sulfonamide type weedicide for further reducing provides novel method, and by product is environmentally friendly, there is important industrial application value.
Realize technical route of the present invention as follows: a kind of preparation method of triazolo pyrimidine sulfydryl type compound, has following steps: by formula II compound
Figure BDA0000475822770000021
Wherein, R 1, R 2for independently hydrogen, halogen, nitro, C separately 1-C 5alkyl, C 1-C 5alkoxyl group;
At the alcohol alkali (III) of 1.0 times of-10.0 times of molar weights
R 3OM (III)
Wherein R 3for C 2-C 12alkyl, M is basic metal;
Under effect, the preferably alcohol alkali of 1.5-3 times of molar weight, resets and replaces in organic solvent at a certain temperature, obtains compound described in formula I through aftertreatment.
Temperature of reaction described in present method is generally carried out at the temperature of-50 DEG C-50 DEG C, and the temperature of 0-30 DEG C is more excellent temperature of reaction.
Present method organic solvent used comprises methyl alcohol, ethanol, acetonitrile, methylene dichloride, ethylene dichloride, toluene, dimethylbenzene, tetrahydrofuran (THF), dioxane, DMSO, DMF, DMAC, NMP, or its mixture.
The present invention adopts a kind of new response strategy, taking formula (II) compound as raw material and alcohol alkali reset substitution reaction prepare compound (I), this new reaction by product is methyl alcohol, efficiently solves thiomethyl alcohol stench problem, is more conducive to suitability for industrialized production.
Embodiment
The following examples further for example understand features more of the present invention, but the content that the present invention protects and scope are not subject to the restriction of following embodiment.
Embodiment 1
The preparation of fluoro-[1,2,4]-triazolo-[1,5-C]-pyrimidine-2 of 5-oxyethyl group-7-(3H) thioketones
By 10.0g(0.048mol, purity 96%) 5-methoxyl group-7-fluoro-[1,2,4]-triazolo-[4,3-C]-pyrimidine-3(2H) thioketones joins in 40g ethanol.Under 0 DEG C of-10 DEG C of condition, 5.4g sodium ethylate is added in above-mentioned solution.Mixture stirs 2h at 0 DEG C-10 DEG C.Then by the concentrated hydrochloric acid acidifying of 9.5g36% for mixture, after-5 DEG C of following 30min of stirring, filter after adding 50g water, and with 20ml cold water and the cold washing with alcohol filter cake of 20ml, be dried and obtain 9.2g target compound, product is rice white solid.
NMR(CDCl 3)δ: 1H:1.47(t,3H),4.69(q,2H),7.04(d,1H).
Embodiment 2
The preparation of chloro-[1,2,4]-triazolo-[1,5-C]-pyrimidine-2 of 5-oxyethyl group-7-(3H) thioketones
By 10.8g(0.048mol, purity 96%) 5-methoxyl group-7-chloro-[1,2,4]-triazolo-[4,3-C]-pyrimidine-3(2H) thioketones joins in 40g ethanol.Under 0 DEG C of-10 DEG C of condition, 5.4g sodium ethylate is added in above-mentioned solution.Mixture stirs 2h at 0 DEG C-10 DEG C.Then by the concentrated hydrochloric acid acidifying of 9.5g36% for mixture, after-5 DEG C of following 30min of stirring, filter after adding 50g water, and with 20ml cold water and the cold washing with alcohol filter cake of 20ml, be dried and obtain 9.5g target compound, product is rice white solid.
Embodiment 3
The preparation of fluoro-[1,2,4]-triazolo-[1,5-C]-pyrimidine-2 of 5-oxyethyl group-8-(3H) thioketones
By 10.0g(0.048mol, purity 96%) 5-methoxyl group-8-fluoro-[1,2,4]-triazolo-[4,3-C]-pyrimidine-3(2H) thioketones joins in 40g ethanol.Under 0 DEG C of-10 DEG C of condition, 5.4g sodium ethylate is added in above-mentioned solution.Mixture stirs 2h at 0 DEG C-10 DEG C.Then by the concentrated hydrochloric acid acidifying of 9.5g36% for mixture, after-5 DEG C of following 30min of stirring, filter after adding 50g water, and with 20ml cold water and the cold washing with alcohol filter cake of 20ml, be dried and obtain 9.2g target compound, product is rice white solid.
Embodiment 4-9
The preparation of reaction preparation 5-fluoro-[1,2,4]-triazolo-[1,5-C]-pyrimidine-2 of oxyethyl group-7-(3H) thioketones under different condition
Embodiment 4-embodiment 9 is with reference to embodiment 1, and raw material drops into and is 10.0g, and reaction conditions and product yield see the following form:
Alcohol alkali Solvent The mol ratio of raw material and alkali Temperature of reaction Product weight
Embodiment 4 Sodium ethylate Ethanol 1:5 0℃ 9.0g
Embodiment 5 Dodecane lithium alkoxide Ethanol 1:10 -50℃ 8.0g
Embodiment 6 Potassium ethylate Acetonitrile 1:10 -50℃ 7.9g
Embodiment 7 Potassium ethylate Methylene dichloride 1:1.1 -10℃ 8.1g
Embodiment 8 Lithium ethoxide DMSO 1:1.8 50℃ 7.5g
Embodiment 9 Sodium ethylate Toluene 1:1.8 50℃ 9.0g

Claims (8)

1. a preparation method for triazolo pyrimidine sulfydryl type compound, is characterized in that: compound (II), under alcohol alkali (III) effect, in organic solvent, reset to substitution reaction and obtained compound (I) under certain temperature,
Wherein the structural formula of compound (I) is:
Figure FDA0000475822760000011
In formula, R 1, R 2for independently hydrogen, halogen, nitro, C separately 1-C 5alkyl, C 1-C 5alkoxyl group, R 3for C 2-C 12alkyl;
The structural formula of compound (II) is:
Figure FDA0000475822760000012
In formula, R 1, R 2for independently hydrogen, halogen, nitro, C separately 1-C 5alkyl, C 1-C 5alkoxyl group;
The structural formula of alcohol alkali (III) is:
R 3OM (III)
R in formula 3for C 2-C 12alkyl, M is basic metal.
2. method according to claim 1, is characterized in that described R 1, R 2for hydrogen or halogen, R 3for C 2-C 5alkyl.
3. method according to claim 1 and 2, is characterized in that described R 1for H, R 2for fluorine, R 3for ethyl.
4. method according to claim 1, is characterized in that R in described alcohol alkali 3for C 2-C 5alkyl, basic metal is one or more in Li, Na, K.
5. method according to claim 1, is characterized in that described compound (II) and the mol ratio of alcohol alkali (III) are that 1:1 is to 1:10.
6. method according to claim 1, is characterized in that described organic solvent is one or more in methyl alcohol, ethanol, acetonitrile, methylene dichloride, ethylene dichloride, toluene, dimethylbenzene, tetrahydrofuran (THF), dioxane, DMSO, DMF, DMAC, NMP.
7. method according to claim 1, is characterized in that described rearrangement substitution reaction temperature is-50-50 DEG C.
8. according to the method described in claim 1 or 7, it is characterized in that described rearrangement substitution reaction temperature is preferably 0 DEG C-30 DEG C.
CN201410089040.8A 2014-03-12 2014-03-12 A kind of preparation method of triazolo pyrimidine mercapto radical-type compound Active CN103880846B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201410089040.8A CN103880846B (en) 2014-03-12 2014-03-12 A kind of preparation method of triazolo pyrimidine mercapto radical-type compound
PCT/CN2015/073741 WO2015135439A1 (en) 2014-03-12 2015-03-06 Triazolo pyrimidine sulfydryl compound preparation method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410089040.8A CN103880846B (en) 2014-03-12 2014-03-12 A kind of preparation method of triazolo pyrimidine mercapto radical-type compound

Publications (2)

Publication Number Publication Date
CN103880846A true CN103880846A (en) 2014-06-25
CN103880846B CN103880846B (en) 2016-09-14

Family

ID=50950011

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410089040.8A Active CN103880846B (en) 2014-03-12 2014-03-12 A kind of preparation method of triazolo pyrimidine mercapto radical-type compound

Country Status (2)

Country Link
CN (1) CN103880846B (en)
WO (1) WO2015135439A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015135439A1 (en) * 2014-03-12 2015-09-17 泸州东方农化有限公司 Triazolo pyrimidine sulfydryl compound preparation method

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995012597A1 (en) * 1993-11-05 1995-05-11 Dowelanco 2-alkoxy-4-hydrazinopyrimidine compounds and their use in the preparation of 5-alkoxy-1,2-4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds
WO1995012595A1 (en) * 1993-11-05 1995-05-11 Dowelanco 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds and their use in the preparation of 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3h)-thione and 3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds
CN1115983A (en) * 1993-11-05 1996-01-31 道伊兰科公司 5-alkoxyl[1,2,4]triazolo[1,5-C]pyrimidine-2(3H)-thione compounds and their use in the preparation of 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-C]-pyrimidine) and 2-chlorosulfonyl-5-alkoxy[1,2,4].....
CN1230961A (en) * 1997-06-26 1999-10-06 道农业科学公司 Process for heterocyclic sulfonyl chloride compounds

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1172934C (en) * 2000-06-16 2004-10-27 美国陶氏益农公司 Process for preparation of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine
CN103880846B (en) * 2014-03-12 2016-09-14 泸州东方农化有限公司 A kind of preparation method of triazolo pyrimidine mercapto radical-type compound

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995012597A1 (en) * 1993-11-05 1995-05-11 Dowelanco 2-alkoxy-4-hydrazinopyrimidine compounds and their use in the preparation of 5-alkoxy-1,2-4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds
WO1995012595A1 (en) * 1993-11-05 1995-05-11 Dowelanco 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2h)-thione compounds and their use in the preparation of 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3h)-thione and 3-hydrocarbylthio-5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine compounds
CN1115983A (en) * 1993-11-05 1996-01-31 道伊兰科公司 5-alkoxyl[1,2,4]triazolo[1,5-C]pyrimidine-2(3H)-thione compounds and their use in the preparation of 2,2'-dithiobis(5-alkoxy[1,2,4]triazolo[1,5-C]-pyrimidine) and 2-chlorosulfonyl-5-alkoxy[1,2,4].....
CN1230961A (en) * 1997-06-26 1999-10-06 道农业科学公司 Process for heterocyclic sulfonyl chloride compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
张梅凤 等: "除草剂双氟磺草胺的合成", 《农药》 *
王胜得 等: "除草剂双氟磺草胺的合成研究", 《农药科学与管理》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015135439A1 (en) * 2014-03-12 2015-09-17 泸州东方农化有限公司 Triazolo pyrimidine sulfydryl compound preparation method

Also Published As

Publication number Publication date
WO2015135439A1 (en) 2015-09-17
CN103880846B (en) 2016-09-14

Similar Documents

Publication Publication Date Title
CN102079725B (en) Method for preparing 2-chloropyrimidine
CN101417962B (en) Method for preparing 2-cyano-3-amino acrylic ester derivates
CN104370915A (en) Preparation method of sildenafil citrate
WO2016088094A1 (en) Process for the preparation of baricitinib and an intermediate thereof
CN106496231B (en) A kind of environment-friendly type preparation method for synthesizing folic acid
CN105646373A (en) Preparation method of 4-amino-2,6-dimethoxypyrimidine
CN101671328A (en) Novel synthesis method of sulfonylurea weedicide
CN103880846A (en) Preparation method of triazolopyrimidine sulfydryl type compound
CN103524493A (en) Nicosulfuron preparation method
CN104650093A (en) Synthesis method of sildenafil analog
CN102875544B (en) Preparation technology of solifenacin succinate
CN104098502B (en) A kind of synthetic method of (S)-Alpha-hydroxy-γ-N-phthaloylamino butyric acid
KR102684954B1 (en) Novel intermediates useful for the synthesis of aminopyrimidine derivatives, process for preparing the same, and process for preparing aminopyrimidine derivatives using the same
CN105037277A (en) Synthesis method of 3,4-dihydropyrimidin/thinatoheterocyclic compound
CN102516133A (en) Preparation method of methanesulfonic acid derivative
CN102757390B (en) Method for preparing 2-methoxy-4-diazanyl-5-fluoropyrimidine
CN104030941B (en) A kind of 3-(4-hydroxy phenyl) synthetic method of propionic acid amide
CN105503853B (en) The synthetic method of cefdinir active thioester
CN104513837A (en) Chiral synthesis method of (R)-1-(3, 5-di (trifluoromethyl) phenyl] ethanol
CN103951669B (en) Synthesis method of Anagliptin key intermediate
CN104496913A (en) Method for preparing 5-substituted-2,4-dimethylsulfenyl pyrimidine
CN101817796A (en) Method for preparing cefotiam side chain
CN105085526B (en) A kind of improved silaenafil preparation method
CN104725323A (en) Synthetic process of 2-methoxyl-4-diazanyl-5-fluoropyrimidine
CN103819411A (en) New preparation method of macitentan intermediate

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant