CN107162986A - A kind of preparation method of the pyrimidine derivatives containing morpholinyl - Google Patents
A kind of preparation method of the pyrimidine derivatives containing morpholinyl Download PDFInfo
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- CN107162986A CN107162986A CN201710401138.6A CN201710401138A CN107162986A CN 107162986 A CN107162986 A CN 107162986A CN 201710401138 A CN201710401138 A CN 201710401138A CN 107162986 A CN107162986 A CN 107162986A
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- prepare compound
- bromopyrimidine
- reaction prepare
- bases
- methyl
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- 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
- C07D239/30—Halogen atoms or nitro radicals
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to organic synthesis field; the special standby preparation method for being related to a kind of i.e. N of the pyrimidine derivatives containing morpholinyl ((base of 2 Bromopyrimidine 5) methyl) 2 morpholine ethamine; using (base of 2 Bromopyrimidine 5) methylamine as initiation material; target product is obtained by acylation, nucleophilic displacement of fluorine, reduction, the compound can enrich organic synthesis molecular building block.
Description
Technical field
The invention belongs to organic synthesis field, a kind of pyrimidine derivatives containing morpholinyl more particularly to are N N- ((2- bromines
Pyrimidine -5- bases) methyl) -2- morpholine ethamine preparation methods.
Technical background
Compound N-((2- Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine, structural formula is：
This compound N-((2- Bromopyrimidine -5- bases) methyl) -2- morpholines ethamine and the derivative of correlation in pharmaceutical chemistry and
There is extensive use in organic synthesis.The synthesis of current N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine is more difficult.
It is easy to get accordingly, it would be desirable to develop a raw material, it is easy to operate, react easily controllable, the suitable synthetic method of overall yield.
The content of the invention
The invention discloses the method that one kind prepares N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine, with (2- bromines
Pyrimidine -5- bases) methylamine be initiation material, obtained by acylation, nucleophilic, reduction, hydrochloric acid salt under target product 5, synthetic route：
In a preferred embodiment, the reagent used in described acylation reaction prepare compound 2 is selected from chloracetyl
Chlorine；Alkali used in described necleophilic reaction prepare compound 3 is selected from potassium carbonate；Described reduction substitution reaction prepare compound 4
Reducing agent used used is selected from lithium aluminium hydride.
In a preferred embodiment, the solvent used in described acylation reaction prepare compound 2 is selected from dichloromethane
Alkane；Solvent used in described necleophilic reaction prepare compound 3 is selected from DMF；Described reduction substitution reaction
Solvent used in prepare compound 4 is selected from tetrahydrofuran.
Beneficial effects of the present invention：There is provided a kind of N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine it is quick,
High-efficiency synthesis method.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent substitution made to the technical characteristic of the present invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1：
(1) synthesis of N- ((2- Bromopyrimidine -5- bases) methyl) -2- chloroacetamides
12g (2- Bromopyrimidine -5- bases) methylamine is added in 120ml dichloromethane, 0 DEG C is cooled to, chloracetyl chloride is added dropwise,
Stirring 3 hours, adds water and is extracted, point liquid, drying, concentration, the isolated 14g N- of residue upper prop ((2- Bromopyrimidines -5-
Base) methyl) -2- chloroacetamides.
(2) synthesis of N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholine acetamides
14g N- ((2- Bromopyrimidine -5- bases) methyl) -2- chloroacetamides are added to 110ml DMFs
In, 6g potassium carbonate and 8g morpholines are added, backflow is reheated and stays overnight, be cooled to room temperature, concentrate, add water and dichloromethane, extract
A point liquid is taken, organic phase is collected, divides silica gel post separation on liquid, drying, concentration, residue to obtain 17g N- ((2- Bromopyrimidine -5- bases) first
Base) -2- morpholine acetamides.
(3) synthesis of N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine
17g N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholino acetamides are added in 150ml tetrahydrofurans, dropped
Temperature is slowly added to 6.5g Lithium Aluminium Hydrides to 0 DEG C, and 0 DEG C is stirred 6 hours, adds water, and filtering, filtrate concentration obtains 12g N- ((2-
Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine.
Claims (3)
1. the method that one kind prepares N- ((2- Bromopyrimidine -5- bases) methyl) -2- morpholine ethamine, with (2- Bromopyrimidine -5- bases) methylamine
For initiation material, target product 4 is obtained by acylation, nucleophilic, reduction, synthetic route is as follows：
2. according to the method described in claim 1, it is characterised in that the reagent used in described acylation reaction prepare compound 2
Selected from chloracetyl chloride；Alkali used in described necleophilic reaction prepare compound 3 be selected from potassium carbonate, sodium hydride, triethylamine, pyridine,
In one kind, preferably potassium carbonate；Reducing agent used used in described reduction substitution reaction prepare compound 4 is selected from boron hydrogen
Change one kind in sodium, potassium borohydride, lithium aluminium hydride, preferably lithium aluminium hydride.
3. according to the method described in claim 1, it is characterised in that the solvent used in described acylation reaction prepare compound 2
One kind in dichloromethane, tetrahydrofuran, dioxane, preferably dichloromethane；Described necleophilic reaction prepares chemical combination
The one kind of solvent in dioxane, DMF, toluene used in thing 3, preferably N, N- dimethyl formyls
Amine；Solvent used in described reduction substitution reaction prepare compound 4 is selected from ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran, dioxy
One kind in six rings, preferably tetrahydrofuran.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710401138.6A CN107162986A (en) | 2017-05-31 | 2017-05-31 | A kind of preparation method of the pyrimidine derivatives containing morpholinyl |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710401138.6A CN107162986A (en) | 2017-05-31 | 2017-05-31 | A kind of preparation method of the pyrimidine derivatives containing morpholinyl |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107162986A true CN107162986A (en) | 2017-09-15 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710401138.6A Pending CN107162986A (en) | 2017-05-31 | 2017-05-31 | A kind of preparation method of the pyrimidine derivatives containing morpholinyl |
Country Status (1)
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| CN (1) | CN107162986A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104230853A (en) * | 2014-08-18 | 2014-12-24 | 湖南华腾制药有限公司 | Preparation method of (p-methylphenyl) methylamine-N-morpholinoethyl hydrochloride |
-
2017
- 2017-05-31 CN CN201710401138.6A patent/CN107162986A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104230853A (en) * | 2014-08-18 | 2014-12-24 | 湖南华腾制药有限公司 | Preparation method of (p-methylphenyl) methylamine-N-morpholinoethyl hydrochloride |
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Application publication date: 20170915 |