CN109503500A - A kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid - Google Patents
A kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid Download PDFInfo
- Publication number
- CN109503500A CN109503500A CN201811539865.XA CN201811539865A CN109503500A CN 109503500 A CN109503500 A CN 109503500A CN 201811539865 A CN201811539865 A CN 201811539865A CN 109503500 A CN109503500 A CN 109503500A
- Authority
- CN
- China
- Prior art keywords
- oxopyrazine
- acetic acid
- reaction
- tert
- added
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/18—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to the synthetic methods of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid.There is no the technical issues of industrializing synthesis route before mainly solving this compound.A kind of technical solution of the present invention: synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid, the following steps are included: the first step, 2- Oxopyrazine is dissolved in nitrogen, in nitrogen-dimethyl acetamide, then potassium carbonate is added, is eventually adding 2- bromo-acetic acid tert-butyl.2- (2- Oxopyrazine -1 (2H)-yl) tert-butyl acetate is obtained after the reaction was completed.Second step, 2- (2- Oxopyrazine -1 (2H)-yl) tert-butyl acetate is dissolved in methylene chloride, then hydrochloric acid/dioxane solution is added, it is post-treated to obtain 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid after reaction is completed.Present invention employs raw materials cheap and easy to get, avoid complicated last handling process, only obtain target molecule by two-step reaction, be easy to amplify.
Description
Technical field
The present invention relates to a kind of practicability synthetic methods of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid.
Background technique
2- (2- Oxopyrazine -1 (2H)-yl) acetic acid, CAS 42352-55-6, synthetic route, only did milligram grade at present
Reaction, taken a sample and done spectral characterization, it cannot be guaranteed that taking target compound with stable yield.
Summary of the invention
The purpose of the present invention is developing a kind of simple, general 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid synthetic method,
The technical issues of mainly solving currently without Industrialized synthesis method.
Technical solution of the present invention: a kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid, including following step
It is rapid:
2- Oxopyrazine is dissolved in nitrogen, in nitrogen-dimethyl acetamide, potassium carbonate is then added, is eventually adding 2- bromine by the first step
Tert-butyl acetate.2- (2- Oxopyrazine -1 (2H)-yl) tert-butyl acetate is obtained after the reaction was completed.
2- (2- Oxopyrazine -1 (2H)-yl) tert-butyl acetate is dissolved in methylene chloride, salt is then added by second step
Acid/dioxane solution, it is post-treated to obtain 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid after reaction is completed.Reaction equation is such as
Under:
。
First step reaction temperature be room temperature, the reaction time 7 hours；Second step reaction temperature is room temperature, is reacted 16 hours.
Beneficial effects of the present invention: rationally, step is simple for reaction process of the present invention design, use it is cheap and easy to get, can advise
The raw material of modelling production avoids complicated last handling process, only obtains target molecule by two-step reaction, be easy to be enlarged into industry
It is combined to, has filled up the synthesis blank of 2- (2- Oxopyrazine -1 (2H)-yl) commercial acetic acid.
Specific embodiment
The synthesis of 2- (2- Oxopyrazine -1 (2H)-yl) tert-butyl acetate
10 g of compound 1 are added in the round-bottomed flask of 1L, are added the nitrogen of 300mL, nitrogen-dimethyl acetamide dissolution, then plus
Enter 17 grams of potassium carbonate, be eventually adding 24 g of compound 2,7 hours are stirred at room temperature in reaction solution.
It is completed to reaction detection, the dilution of 900mL ethyl acetate is added in filtering removal potassium carbonate, respectively with 300mL water extraction two
Secondary, organic phase is washed twice with saturated salt solution 300mL, and organic phase is dry by anhydrous sodium sulfate, is concentrated by Rotary Evaporators
Obtain crude product.Crude product passes through silica gel column purification, obtains 18.3 g of compound 3, yield 83%.
1H NMR (400MHz, DMSO-d6) Shift = 8.057 (s, 1H), 7.645-7.634 (d, J=
4.4 Hz, 1H), 7.371-7.360 (d. J= 4.4 Hz, 1H), 4.617 (s, 2H), 1.426 (S, 9H)。
The synthesis of the synthesis of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid
6 g of compound 3 are added to 250mL round-bottomed flask, the dissolution of 50mL methylene chloride is added, 4M hydrochloric acid/dioxy is then added
Six ring 21mL, are stirred at room temperature, and react 16 hours.The precipitating of precipitation is collected by filtration, and methylene chloride washing obtains 4 after dry
G of compound 4, yield 92%.
1H NMR (400MHz, DMSO-d6) Shift = 8.173-8.157 (m, 1H), 7.695-7.666 (m,
1H), 7.459-7.441 (m, 1H), 4.761-4.755 (m, 2H)。
Claims (3)
1. a kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid, it is characterized in that: the following steps are included: the first step,
2- Oxopyrazine is dissolved in nitrogen, in nitrogen-dimethyl acetamide, potassium carbonate is then added, is eventually adding 2- bromo-acetic acid tert-butyl,
2- (2- Oxopyrazine -1 (2H)-yl) tert-butyl acetate is obtained after the reaction was completed；Second step, by 2- (2- Oxopyrazine -1 (2H) -
Base) tert-butyl acetate is dissolved in methylene chloride, hydrochloric acid/dioxane solution is then added, after reaction is completed, post-treated
To 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid；Reaction equation is as follows:
。
2. a kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid according to claim 1, it is characterized in that:
First step reaction temperature be room temperature, the reaction time 7 hours.
3. a kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid according to claim 1, it is characterized in that:
Second step reaction temperature be room temperature, the reaction time 16 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811539865.XA CN109503500A (en) | 2018-12-17 | 2018-12-17 | A kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811539865.XA CN109503500A (en) | 2018-12-17 | 2018-12-17 | A kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109503500A true CN109503500A (en) | 2019-03-22 |
Family
ID=65753479
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811539865.XA Pending CN109503500A (en) | 2018-12-17 | 2018-12-17 | A kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109503500A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009123870A1 (en) * | 2008-04-04 | 2009-10-08 | Merck & Co., Inc. | Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists |
| CN102391255A (en) * | 2008-04-04 | 2012-03-28 | 默沙东公司 | Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists |
-
2018
- 2018-12-17 CN CN201811539865.XA patent/CN109503500A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009123870A1 (en) * | 2008-04-04 | 2009-10-08 | Merck & Co., Inc. | Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists |
| CN102391255A (en) * | 2008-04-04 | 2012-03-28 | 默沙东公司 | Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105622535B (en) | A kind of preparation method of LCZ696 | |
| JP6948419B2 (en) | New manufacturing method for chromanon derivatives | |
| CN105814020A (en) | Substituted nicotinamide derivatives as kinase inhibitors | |
| CN105175401A (en) | Preparation method of brexpiprazole | |
| CN106256824B (en) | Preparation method of high-purity delafloxacin meglumine salt | |
| CN103772278A (en) | Important tetrahydroisoquinoline derivative midbody and synthesis method thereof | |
| TWI703163B (en) | Method for preparing sugammadex sodium and crystalline form thereof | |
| CN110872262A (en) | Synthesis method of cariprazine | |
| JP2007503476A (en) | Improved production of rebamipide | |
| CN109867673B (en) | Method for synthesizing palbociclib | |
| CN109503500A (en) | A kind of synthetic method of 2- (2- Oxopyrazine -1 (2H)-yl) acetic acid | |
| CN103665084A (en) | Method for preparing abiraterone acetate | |
| CN106892803B (en) | Preparation method of 2, 6-dichloro-3-fluorobenzaldehyde and preparation method of fluoroquinolone compound | |
| CN107176906A (en) | A kind of synthetic method of substitution indone | |
| CN111349045A (en) | Synthetic method of lenvatinib and novel intermediate | |
| CN112645880B (en) | Synthetic method of enzalutamide | |
| CN105085595B (en) | A kind of method of deacylation base protection 2,6 halosubstituted purine nucleosides of synthesis | |
| CN110903211B (en) | Preparation method of L-theanine | |
| CN111269094B (en) | Preparation method of 2-bromo-1, 3-dimethoxybenzene | |
| CN106045995A (en) | Synthesizing method of 5-bromine-1H-pyrrolo[2,3-b]pyridine | |
| CN112125790A (en) | Synthesis method of 7-chloro-1-naphthaldehyde | |
| JP5501054B2 (en) | Method for producing 3,3-diaminoacrylic acid (1-diphenylmethylazetidin-3-yl) ester acetate | |
| CN103880730A (en) | Chemical synthesis method of 7-nitroindole-3-tert butyl formate | |
| CN107353275B (en) | Synthesis method of xanthene-9-formic acid | |
| CN103450182B (en) | Preparation and purification methods of Retapamulin |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190322 |