CN103980249B - A kind of process for purification of SYR-322 - Google Patents

A kind of process for purification of SYR-322 Download PDF

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Publication number
CN103980249B
CN103980249B CN201410236391.7A CN201410236391A CN103980249B CN 103980249 B CN103980249 B CN 103980249B CN 201410236391 A CN201410236391 A CN 201410236391A CN 103980249 B CN103980249 B CN 103980249B
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syr
methyl
purification
dihydro
cyanobenzene
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CN103980249A (en
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徐自奥
李德刚
李晓祥
邓勤军
赵永海
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XINXING MEDICAMENT DEVELOPMENT Co Ltd ANHUI PROV
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XINXING MEDICAMENT DEVELOPMENT Co Ltd ANHUI PROV
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

The invention discloses a kind of process for purification of SYR-322, this process for purification with the chloro-3-6-Methyl Uracil of 6-, 2-cyano-benzyl bromide for starting raw material, SYR-322 crude product is obtained successively through two step amination reactions and a step salt-forming reaction, then by the SYR-322 crude product that obtains under benzoic existence, in methyl alcohol, crystallization obtains SYR-322 fine work.This process for purification can improve yield and the purity of SYR-322 effectively, and simultaneously simple to operate, cost is low.

Description

A kind of process for purification of SYR-322
Technical field
The invention belongs to pharmaceutical synthesis field, be specifically related to a kind of process for purification of SYR-322.
Background technology
SYR-322 (AlogliptinBenzoate), chemical name is 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] benzonitrile benzoic acid salt, structure, as shown in formula I, is a kind of DPP-IV inhibitor of Japanese military field pharmaceutical development.It promotes the concentration dependent insulin secretion with sugar by the plasma concentration improving GLP-1 in body, maintains the level of glucagon-1 peptide and glucose-dependent-insulinotropic peptide in body, increases the secretion of Regular Insulin, thus plays hypoglycemic curative effect.
Publication number is the preparation method that the Chinese patent application of CN103467455A discloses a kind of SYR-322, the method with 6-methyl-3-chlorouracil and adjacent cyano group bromobenzene for starting raw material, SYR-322 is obtained through three-step reaction, in this preparation method, (R)-3-amino-piperadine is replaced to react with the imines that phenyl aldehyde and the reaction of (R)-3-amino piperidine generate.
Publication number is the preparation technology that the Chinese patent application of CN102942556A discloses a kind of SYR-322, with 6-methyl-3-chlorouracil for raw material, obtained 2-(the chloro-3-methyl-2 of 6-is reacted with 2-cyano group bromobenzene, 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene, then with (R)-3-Boc-amino piperidine generation substitution reaction, after having reacted, slough Boc, then obtain phenyl aldehyde Egelieting with phenylformic acid salify.
Publication number is the preparation method that the Chinese patent application of CN103193762A discloses a kind of SYR-322, with 6-chlorouracil for starting raw material, with adjacent chloro benzyl bromine reaction, obtain 2-((6-chloro-2,4-dioxy-3,4-dihydro-2H-pyrimidine-1-base) methyl) cyanobenzene, methylate with methyl iodide again, obtain 2-((6-chloro-3-methyl-2,4-dioxy-3,4-dihydro-2H-pyrimidine-1-base) methyl) cyanobenzene, then react with (R)-3-Boc-amino piperidine, slough Boc, then with phenylformic acid salify, obtain SYR-322.
Summary of the invention
The invention provides a kind of process for purification of SYR-322, the SYR-322 yield that this process for purification obtains and purity high, and simple to operate.
A process for purification for SYR-322, comprises the steps:
(1) in aromatic hydrocarbon solvent, the heating of the chloro-3-6-Methyl Uracil of 6-, 2-cyano-benzyl bromide and the first organic bases is reacted, 2-(the chloro-3-methyl-2 of 6-is obtained through process later after reacting completely, 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene;
(2) in the first alcoholic solvent, 2-(the chloro-3-methyl-2 of 6-that step (1) obtains, 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene, (R)-3-amino piperidine two hydrochloric acid and the second organic bases heating react, described 2-[[6-[(3R)-3-amino-piperidino]-3 is obtained through process later after reacting completely, 4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene;
(3) by 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene joins in the second alcoholic solvent, after heated and stirred is dissolved, add phenylformic acid to react, to reaction solution cooling after reacting completely, separate out solid, drying obtains SYR-322 crude product;
(4) rising temperature for dissolving after the SYR-322 crude product, phenylformic acid and the methanol mixed that step (3) are obtained, then gac is added, heated and stirred 0.5 ~ 1 hour, take advantage of hot pressing to filter and obtain filtrate, cool to-5 ~ 5 DEG C, stirring and crystallizing, suction filtration, drying obtain described SYR-322 fine work.
This preparation method's chemical equation is expressed as follows:
In the step (4) of process for purification of the present invention, be raw material with SYR-322, add appropriate phenylformic acid, purify in specific solvent, the SYR-322 yield obtained and purity high, and simple to operate
In step (1), described aromatic hydrocarbon solvent is at least one in toluene, p-Xylol, o-Xylol, m-xylene and trimethylbenzene; Be preferably toluene;
The first described organic bases is diisopropyl ethyl amine, triethylamine or tri-n-butylamine; Be preferably tri-n-butylamine;
As further preferred, described aromatic hydrocarbon solvent is toluene, the first described organic bases is tri-n-butylamine, now, yield and the purity of 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene obtained are higher, directly can carry out subsequent step, and not need to carry out extra purification process.
In step (1), the mol ratio of the chloro-3-6-Methyl Uracil of described 6-, 2-cyano-benzyl bromide and the first organic bases is 1:1 ~ 1.5:1 ~ 2.
In step (1), temperature of reaction is 80 ~ 85 DEG C, and the reaction times is 5 ~ 6 hours.
As preferably, in step (1), described post-processing step is as follows: reaction solution is cooled to-5 ~ 5 DEG C, add water, stir and separate out solid, suction filtration drying obtains described 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene;
The quality of described water is 2 ~ 3 times of the chloro-3-6-Methyl Uracil of 6-, most preferably is 2 times.Wherein, the consumption of water is too much, and the product purity separated out can be caused to reduce, and the consumption of water is very few, can reduce the yield of product.
2-(the chloro-3-methyl-2 of 6-obtained of step (1), 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene through HPLC be up to the standards (purity must not lower than 98.0%) next step operation can be dropped into, as defective, dehydrated alcohol recrystallization can be used.
In step (2), the first described alcoholic solvent is preferably C 1~ C 5alkyl alcohol, more preferably Virahol;
The second described organic bases is preferably diisopropyl ethyl amine, triethylamine or tri-n-butylamine; More preferably triethylamine;
As further preferred, the first described alcoholic solvent is Virahol, second organic bases is triethylamine, now, yield and the purity of 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene obtained are higher, directly can carry out subsequent step, and not need to carry out extra purification process.
In step (2), temperature of reaction is 60 ~ 70 DEG C, and the reaction times is 16 ~ 18 hours.
In step (2), described post-processing step is as follows: by reaction solution removal of solvent under reduced pressure, add water fully to stir, filtration obtains filtrate, filtrate regulates pH to 9 ~ 11 with alkali, dichloromethane extraction, and organic phase is dry, filter, concentratedly obtain described 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene;
The quality of water used is 30 ~ 50 times of 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene used, is preferably 25 times.
The product of step (2) can drop into next step operation through be up to the standards (purity is greater than 98.0%), as defective, and available anhydrous alcohol solution, petroleum ether and stirring purifying.
As preferably, in step (3), temperature of reaction is 65 ~ 75 DEG C, and the reaction times is 5 ~ 6 hours.
In step (3), the second described alcoholic solvent is ethanol, and cooling temperature is-5 ~ 5 DEG C, and the yield of the SYR-322 crude product now obtained is higher, and impurity is less, the purifying of a step after being convenient to.
As preferably, in step (4), described SYR-322 crude product and benzoic mol ratio are 1:0.05 ~ 0.3, most preferably are 1:0.2.
Described SYR-322 crude product and the mass ratio of methyl alcohol are preferably 1:5 ~ 10; Most preferably be 1:8.
As preferably, in step (4), described recrystallization temperature is-5 ~ 5 DEG C, more preferably 0 ~ 5 DEG C.
Gac is added during heated and stirred in step (4).
Compared with the existing technology, the SYR-322 dissolving crude product that obtains in methyl alcohol, is carried out purifying, effectively can improve the purity of SYR-322 by the present invention under benzoic existence; Whole route need not be simple to operate simultaneously, need not cross column purification, be convenient to suitability for industrialized production.
Embodiment
Embodiment 1
(1) at room temperature, by chloro-for 6-3-6-Methyl Uracil (160g, 1mol), 2-cyano-benzyl bromide (243g, 1.24mol) with tri-n-butylamine (275g, 1.5mol) add to successively in reactor with toluene (800mL), stir 10 minutes, continue stir and be warming up to 80 DEG C, 80 DEG C of reaction 5h (HPLC monitors reaction and carries out degree), after reaction terminates, stopped reaction is cooled to less than 5 DEG C, add 320g purified water, and stir 40 minutes at 0 ~ 5 DEG C, there is a large amount of solid to separate out, suction filtration.Filter cake, in 80 ± 5 DEG C of oven dry, obtains faint yellow solid 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene 236.5g, HPLC purity: 98.5%, yield: 86%.
(2) 2-(the chloro-3-methyl-2 of 6-step (1) obtained, 4-dioxo-3, 4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene 236.5g, (R)-3-amino piperidine two hydrochloric acid (223g, 1.29mol), Virahol 1000mL and triethylamine (261g, 2.58mol) add to successively in reactor, stir 20 minutes, continue to stir and be warming up to 65 DEG C of reactions 17 hours (HPLC monitors reaction and carries out degree), after reaction terminates, by reaction solution in 60 ± 5 DEG C of concentrating under reduced pressure solvents to dry, add purified water 2500mL, stir 20 minutes, there is undissolved solid, static 1 hour, filter, the purified water that wet cake adds 5000mL again stirs 10 minutes, suction filtration, twice filtrate merges adjusts pH=10 ± 0.5 with 1mol/L sodium hydroxide solution, dichloromethane extraction, separate dichloromethane layer, dichloromethane layer anhydrous magnesium sulfate drying, filter, filtrate 50 ± 5 DEG C of underpressure distillation, obtain faint yellow solid 2-[[6-[(3R)-3-amino-piperidino]-3, 4-dihydro-3-methyl-2, 4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene 248g, yield: 85%, purity 98.2%.
(3) the 2-[[6-[(3R)-3-amino-piperidino]-3 step (2) obtained, 4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene 248g and ethanol 1000mL adds in reactor, and stir 10 minutes, add and be warming up to 70 ± 5 DEG C, add phenylformic acid (134g, 1.09mol), insulation reaction 6 hours, is cooled to room temperature, reaction solution is cooled to less than 5 DEG C, stirs 12h.Have a large amount of white solid to separate out, suction filtration, 70 ± 5 DEG C of heat-wind circulate dryings 4 ~ 5 hours, obtain off-white color SYR-322 crude product 322g, yield: 82%, purity is 98.9%.
(4) SYR-322 crude product 322g, phenylformic acid 18g and methyl alcohol 2000mL that step (3) obtains are added in refining kettle, be warming up to 60 ± 5 DEG C and make dissolving, stirring and dissolving, slowly add gac, holding temperature 60 ± 5 DEG C stirs half an hour, the hot pressing of titanium pump air is filtered, filtrate is depressed in crystallization still, opens and stirs and cold-trap valve, cool to less than 5 DEG C, stirring and crystallizing 3 hours, suction filtration, 70 ± 5 DEG C of heat-wind circulate dryings 4 hours, obtain white SYR-322 fine work 290g, yield: 90%, HPLC purity is 100%.m.p:180.6℃～182.5℃；IR(νcm-1)3085，2954，2860，2229，1698，1652，1547，1448，1374，1230，1134，950，830，769，713。1H-NMR，δ：1.569～1.613(m，2H)；1.757(s，1H)；2.014～2.033(s，1H)；2.728(s，1H)；2.882～2.968(m，2H)；3.077(s，3H)；3.310～3.391(m，2H)；5.094～5.212(q，2H)；5472(s，1H)；7.247～7.267(d，1H)；7.341～7.447(m，4H)；7.555～7.594(m，1H)；7.676～7.696(d，1H)；7.763～7.783(d，2H)。
Embodiment 2
Step (1) ~ (3) are identical with embodiment 1, and difference is that the operation of step (4) is as follows:
The SYR-322 crude product 322g, phenylformic acid 9g and the methyl alcohol 2000mL that step (3) are obtained add in refining kettle, be warming up to 60 ± 5 DEG C and make dissolving, stirring and dissolving, slowly add gac, holding temperature 60 ± 5 DEG C stirs half an hour, the hot pressing of titanium pump air is filtered, filtrate is depressed in crystallization still, opens and stirs and cold-trap valve, cool to less than 5 DEG C, stirring and crystallizing 3 hours, suction filtration, 70 ± 5 DEG C of heat-wind circulate dryings 4 hours, obtain white SYR-322 fine work 284g, yield: 88%, HPLC purity is 99.7%.
Embodiment 3
Step (1) ~ (3) are identical with embodiment 1, and difference is that the operation of step (4) is as follows:
The SYR-322 crude product 322g, phenylformic acid 9g and the methyl alcohol 1500mL that step (3) are obtained add in refining kettle, be warming up to 60 ± 5 DEG C and make dissolving, stirring and dissolving, slowly add gac, holding temperature 60 ± 5 DEG C stirs half an hour, the hot pressing of titanium pump air is filtered, filtrate is depressed in crystallization still, opens and stirs and cold-trap valve, cool to less than 5 DEG C, stirring and crystallizing 3 hours, suction filtration, 70 ± 5 DEG C of heat-wind circulate dryings 4 hours, obtain white SYR-322 fine work 297g, yield: 92%, HPLC purity is 99.6%.
Embodiment 4
(1) at room temperature, by chloro-for 6-3-6-Methyl Uracil (160g, 1mol), 2-cyano-benzyl bromide (243g, 1.24mol) with triethylamine (151g, 1.5mol) add to successively in reactor with dimethylbenzene (800mL), stir 10 minutes, continue stir and be warming up to 80 DEG C, 80 DEG C of reaction 5h (HPLC monitors reaction and carries out degree), after reaction terminates, stopped reaction is cooled to less than 5 DEG C, add 320g purified water, and stir 40 minutes at 0 ~ 5 DEG C, there is a large amount of solid to separate out, suction filtration.Filter cake, in 80 ± 5 DEG C of oven dry, obtains faint yellow solid 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene 222g, HPLC purity: 94.6%, yield: 81%.
The faint yellow solid 222g obtained is joined in dehydrated alcohol 800mL, is heated to backflow, is then cooled to 0 ~ 5 DEG C, hold over night, has a large amount of solid to separate out, after filtration, use a small amount of absolute ethanol washing, obtain faint yellow solid 205g, HPLC purity 98.5%.
Comparative example 1
Step (1) ~ (3) are identical with embodiment 1, and difference is that the operation of step (4) is as follows:
The SYR-322 crude product 322g obtain step (3) and methyl alcohol 2000mL adds in refining kettle, be warming up to 60 ± 5 DEG C and make dissolving, stirring and dissolving, slowly add gac, holding temperature 60 ± 5 DEG C stirs half an hour, the hot pressing of titanium pump air is filtered, filtrate is depressed in crystallization still, opens and stirs and cold-trap valve, cool to less than 5 DEG C, stirring and crystallizing 3 hours, suction filtration, 70 ± 5 DEG C of heat-wind circulate dryings 4 hours, obtain white SYR-322 fine work 278g, yield: 86%, HPLC purity is 99.2%.This comparative example shows do not adding in benzoic situation, and the yield of product is lower, and the raising of purity is also not obvious.
Comparative example 2
Step (1) ~ (3) are identical with embodiment 1, and difference is that the operation of step (4) is as follows:
The SYR-322 crude product 322g, phenylformic acid 18g and the ethanol 2000mL that step (3) are obtained add in refining kettle, be warming up to 60 ± 5 DEG C and make dissolving, stirring and dissolving, slowly add gac, holding temperature 60 ± 5 DEG C stirs half an hour, the hot pressing of titanium pump air is filtered, filtrate is depressed in crystallization still, opens and stirs and cold-trap valve, cool to less than 5 DEG C, stirring and crystallizing 3 hours, suction filtration, 70 ± 5 DEG C of heat-wind circulate dryings 4 hours, obtain white SYR-322 fine work 274g, yield: 85%, HPLC purity is 99.0%.After this comparative example shows that methyl alcohol is replaced to ethanol, the raising of purity is not obvious.

Claims (7)

1. a process for purification for SYR-322, is characterized in that, comprises the steps:
(1) in aromatic hydrocarbon solvent, the heating of the chloro-3-6-Methyl Uracil of 6-, 2-cyano-benzyl bromide and the first organic bases is reacted, 2-(the chloro-3-methyl-2 of 6-is obtained through process later after reacting completely, 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene;
(2) in the first alcoholic solvent, 2-(the chloro-3-methyl-2 of 6-that step (1) obtains, 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene, (R)-3-amino piperidine two hydrochloric acid and the second organic bases heating react, 2-[[6-[(3R)-3-amino-piperidino]-3 is obtained through process later after reacting completely, 4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene;
(3) by 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene joins in the second alcoholic solvent, after heated and stirred is dissolved, add phenylformic acid to react, to reaction solution cooling after reacting completely, separate out solid, drying obtains SYR-322 crude product;
(4) rising temperature for dissolving after the SYR-322 crude product, phenylformic acid and the methanol mixed that step (3) are obtained, then gac is added, heated and stirred 0.5 ~ 1 hour, press filtration while hot obtains filtrate, cool to-5 ~ 5 DEG C, stirring and crystallizing, suction filtration, drying obtain SYR-322 fine work;
In step (2), the first described alcoholic solvent is Virahol; The second described organic bases is triethylamine;
In step (4), described SYR-322 crude product and benzoic mol ratio are 1:0.05 ~ 0.2, and described SYR-322 crude product and the mass ratio of methyl alcohol are 1:5 ~ 10, and described recrystallization temperature is-5 ~ 5 DEG C.
2. the process for purification of SYR-322 according to claim 1, is characterized in that, in step (1), described aromatic hydrocarbon solvent is at least one in toluene, p-Xylol, o-Xylol, m-xylene and trimethylbenzene;
The first described organic bases is diisopropyl ethyl amine, triethylamine or tri-n-butylamine.
3. the process for purification of SYR-322 according to claim 1, is characterized in that, in step (1), temperature of reaction is 80 ~ 85 DEG C, and the reaction times is 5 ~ 6 hours.
4. the process for purification of SYR-322 according to claim 1, it is characterized in that, in step (1), described post-processing step is as follows: reaction solution is cooled to-5 ~ 5 DEG C, add water, stir and separate out solid, suction filtration drying obtains described 2-(the chloro-3-methyl-2 of 6-, 4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene;
The quality of water used is 2 ~ 3 times of the chloro-3-6-Methyl Uracil of 6-.
5. the process for purification of SYR-322 according to claim 1, it is characterized in that, in step (2), described post-processing step is as follows: by reaction solution removal of solvent under reduced pressure, add water fully to stir, filtration obtains filtrate, filtrate regulates pH to 9 ~ 11 with alkali, dichloromethane extraction, organic phase is dry, filter, concentratedly obtain described 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxo-1 (2H)-pyrimidyl] methyl] cyanobenzene;
The quality of water used is 30 ~ 50 times of 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-ylmethyl)-cyanobenzene used.
6. the process for purification of SYR-322 according to claim 1, is characterized in that, in step (3), temperature of reaction is 65 ~ 75 DEG C, and the reaction times is 5 ~ 6 hours.
7. the process for purification of SYR-322 according to claim 1, is characterized in that, in step (3), the second described alcoholic solvent is ethanol, and cooling temperature is-5 ~ 5 DEG C.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101360723A (en) * 2005-09-16 2009-02-04 武田药品工业株式会社 Process for the preparation of pyrimidinedione derivatives
CN102942556A (en) * 2012-12-04 2013-02-27 成都天翼医药科技有限公司 Preparation technique of alogliptin benzoate

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101133363B (en) * 2005-06-20 2011-04-20 凸版印刷株式会社 Colored alkali-developable photosensitive resin composition and color filters made by using the same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101360723A (en) * 2005-09-16 2009-02-04 武田药品工业株式会社 Process for the preparation of pyrimidinedione derivatives
CN102942556A (en) * 2012-12-04 2013-02-27 成都天翼医药科技有限公司 Preparation technique of alogliptin benzoate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
苯甲酸阿格列汀的合成;刘昭文等;《海峡药学》;20111231;第23卷(第9期);第214-215页 *

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