CN112359079A - Preparation method of imatamine - Google Patents
Preparation method of imatamine Download PDFInfo
- Publication number
- CN112359079A CN112359079A CN202011248048.6A CN202011248048A CN112359079A CN 112359079 A CN112359079 A CN 112359079A CN 202011248048 A CN202011248048 A CN 202011248048A CN 112359079 A CN112359079 A CN 112359079A
- Authority
- CN
- China
- Prior art keywords
- imatamine
- nitroreductase
- preparation
- reaction
- coenzyme
- 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
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 20
- 102000004459 Nitroreductase Human genes 0.000 claims abstract description 19
- 108020001162 nitroreductase Proteins 0.000 claims abstract description 19
- 239000005515 coenzyme Substances 0.000 claims abstract description 15
- OJITWRFPRCHSMX-UHFFFAOYSA-N n-(2-methyl-5-nitrophenyl)-4-pyridin-3-ylpyrimidin-2-amine Chemical compound CC1=CC=C([N+]([O-])=O)C=C1NC1=NC=CC(C=2C=NC=CC=2)=N1 OJITWRFPRCHSMX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000006911 enzymatic reaction Methods 0.000 claims abstract description 6
- 230000003197 catalytic effect Effects 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- 239000002904 solvent Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 6
- 102000016938 Catalase Human genes 0.000 claims description 4
- 108010053835 Catalase Proteins 0.000 claims description 4
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical group NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- XJLXINKUBYWONI-NNYOXOHSSA-O NADP(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-O 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 19
- 239000002994 raw material Substances 0.000 abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 6
- 125000003277 amino group Chemical group 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 3
- 239000012535 impurity Substances 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000000967 suction filtration Methods 0.000 description 10
- 238000001514 detection method Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- 230000002349 favourable effect Effects 0.000 description 4
- 238000009776 industrial production Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229960002411 imatinib Drugs 0.000 description 3
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 229960003685 imatinib mesylate Drugs 0.000 description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- DSBIJCMXAIKKKI-UHFFFAOYSA-N 5-nitro-o-toluidine Chemical compound CC1=CC=C([N+]([O-])=O)C=C1N DSBIJCMXAIKKKI-UHFFFAOYSA-N 0.000 description 1
- 241001453380 Burkholderia Species 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
- C12P17/165—Heterorings having nitrogen atoms as the only ring heteroatoms
Abstract
The invention relates to a preparation method of imatamine, belonging to the technical field of drug synthesis. In order to solve the problem of low yield of the existing product, the method for preparing the imatamine comprises the steps of converting a compound of a formula II, namely N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine into the imatamine through an enzymatic reaction under the action of a catalytic amount of nitroreductase and coenzyme; the nitroreductase is shown by SEQ NO1. The method can effectively convert the nitro group into the amino group efficiently, and does not generate other byproducts due to side reaction of the raw materials in the reaction process, so that the method has the advantages of low impurity content and high product conversion rate, and the product yield reaches more than 97%.
Description
Technical Field
The invention relates to a preparation method of imatamine, belonging to the technical field of drug synthesis.
Background
Imatinib mesylate is a first generation tyrosine kinase inhibitor, can specifically block signal transduction of chronic myelogenous leukemia, thereby blocking proliferation of tumor cells, and is clinically used for treating Philadelphia chromosome positive chronic myelogenous leukemia and gastrointestinal stromal tumor patients.
Currently, N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine is mainly used as an intermediate of imatinib mesylate to obtain corresponding imatinib through palladium-carbon hydrogenation reduction, but catalysts adopted in the method, such as palladium-carbon, are expensive, a hydrogenation process is dangerous, and the obtained product is low in yield and purity and is not suitable for industrial production; some of them are also the corresponding immamine obtained by reducing N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine with hydrazine hydrate, however, the hydrazine hydrate used therein is toxic and pollutes the environment, which is not favorable for green production, and the yield and purity of the obtained product are low, which is not suitable for industrial production. And some are synthesized by reducing N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine with zinc or iron. The method adopts metal catalysis, and the wastewater generated in post-treatment is not easy to treat and is not suitable for industrial production; the existing method using 2-amino-4-nitrotoluene as a raw material has the disadvantages of long reaction steps, high operation difficulty, low yield of the obtained product and unsuitability for industrial production.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method of imatamine, aiming at solving the problems of long reaction route, high cost and low product yield in the prior art.
The invention aims to realize the following technical scheme, and the preparation method of the imatamine comprises the following steps:
converting the compound N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine shown in the formula II into the compound imatamine shown in the formula I through an enzymatic reaction under the action of catalytic amount of nitroreductase and coenzyme;
the nitroreductase is shown by SEQ ID NO1.
According to the invention, the specific sequence nitroreductase is adopted to reduce the nitro group in the raw material by the biological enzyme method, and the nitro group can be effectively and efficiently converted into amino group in the coexistence of coenzyme, and the raw material can not generate side reaction to generate other byproducts in the reaction process, so that the method has the advantages of low impurity content and high product conversion rate; meanwhile, due to the adoption of the biological enzyme method for synthesis, a large amount of acid is not needed for post-treatment, so that the generation of a large amount of high-salt waste liquid is effectively avoided, and the effects of high-cost catalysts such as expensive palladium carbon and the like are not needed; in addition, the corresponding product can be obtained only by one-step reduction, and the specific reaction route is short, so that the loss of the intermediate process can be reduced, and the effect of high product yield is achieved.
In the above-mentioned method for producing immamine, the reaction is preferably carried out in a mixed solvent of water and an alcohol solvent. The nitroreductase system with the sequence is adopted for carrying out the enzymatic reaction, so that the reaction can carry out high-efficiency reaction conversion in a water and alcohol solvent system, and the adopted alcohol solvent has low risk and is more favorable for subsequent treatment and recovery. As a further preference, the alcoholic solvent is selected from methanol or ethanol. More preferably, the mass ratio of the alcohol solvent to the water is 1: 4.0-6.0. The reaction can be efficiently carried out only by adopting a small amount of alcohol solvent, and the most of the adopted solvent is water, so that the treatment is more favorable.
In the above method for producing immamine, the coenzyme is preferably a catalase. Can provide hydrogen to effectively convert nitro into amino group in the reduction process, and better ensures the conversion rate of the reaction and the purity and quality requirements of the product. As a further preference, the catalase is selected from NAD+Or NADP+。
In the above method for producing immamine, the temperature of the enzymatic reaction is preferably 30 ℃ to 40 ℃. The nitroreductase and the coenzyme system can be used for carrying out the reaction under mild reaction conditions, and are more favorable for operation.
In the above method for preparing immamine, the nitroreductase is preferably used in an amount of 3% to 5% of the compound of formula ii. The catalytic amount of nitroreductase has better catalytic effect, and has the advantages of high conversion rate and high product purity content.
The concrete reaction equation of the above reaction is as follows:
in summary, compared with the prior art, the invention has the following advantages:
the nitro-reductase with a specific sequence is adopted to reduce the nitro in the raw materials and effectively convert the nitro into amino in the coexistence of coenzyme, and the raw materials are not subjected to side reaction to generate other byproducts in the reaction process, so that the method has the advantages of low impurity content and high product conversion rate, and the product yield is over 97%.
Detailed Description
The technical solution of the present invention is further specifically described below by way of specific examples, but the present invention is not limited to these examples.
Example 1
Adding 100g of water and 20g of ethanol into a clean reactor in sequence, adding 50g of raw material N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine, adopting 2g of nitroreductase shown in SEQ ID NO1 and 0.2g of coenzyme, stirring, slowly heating to 37 ℃ for reaction and heat preservation for 2 hours, after the reaction is finished, performing suction filtration, collecting filtrate, performing reduced pressure distillation to remove solvent ethanol, performing suction filtration, and drying to obtain a corresponding product 44.1g of imatamine, wherein the yield is 97.8%, and the content of liquid phase (HPLC) detection is 99.5%.
Example 2
100g of water, 20g of ethanol and 50g of N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine are sequentially added into a clean reactor, 2g of nitroreductase shown in SEQ ID NO1 and 0.2g of coenzyme are adopted, stirring is carried out, the temperature is slowly increased to about 35 ℃ for reaction and heat preservation for 2 hours, suction filtration is carried out, solvent ethanol is removed by distillation, suction filtration and drying are carried out, and a corresponding product 44.0g of immamine is obtained, the yield is 97.6%, and the content is 99.6% by liquid phase (HPLC) detection.
Example 3
100g of water, 20g of methanol and 50g of N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine are sequentially added into a clean reactor, 2g of nitroreductase shown in SEQ ID NO1 and 0.2g of coenzyme are adopted, the temperature is raised to about 37 ℃ for reaction and heat preservation for 2 hours, the mixture is subjected to suction filtration, solvent ethanol is removed by distillation, the suction filtration and drying are carried out, and a corresponding product 44.3g of imatamine is obtained, the yield is 98.2%, and the content is 99.5% by liquid phase (HPLC) detection.
Example 4
80g of water, 20g of ethanol and 50g of N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine are sequentially added into a clean reactor, 2.5g of nitroreductase shown in SEQ ID NO1 and 0.25g of coenzyme are adopted, and the coenzyme is NAD+Stirring, slowly heating to about 37 ℃, carrying out reaction and heat preservation for 2.5h, carrying out suction filtration, distilling to remove a solvent ethanol, carrying out suction filtration, and drying to obtain a corresponding product 43.8g of imatinib, wherein the yield is 97.2%, and the content is 99.7% by liquid phase (HPLC) detection.
Example 5
120g of water, 20g of ethanol and 50g of N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine are sequentially added into a clean reactor, 3.0g of nitroreductase shown in SEQ ID NO1 and 0.3g of coenzyme are adopted, and the coenzyme is NAD+Stirring, slowly heating to about 40 ℃, carrying out reaction and heat preservation for 2.0h, carrying out suction filtration, distilling to remove a solvent ethanol, carrying out suction filtration, and drying to obtain a corresponding product 44.3g of imatinib, wherein the yield is 98.3%, and the content is 99.6% by liquid phase (HPLC) detection.
The specific embodiments described herein are merely illustrative of the spirit of the invention. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit or ambit of the invention as defined in the appended claims.
While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.
Sequence listing
<110> Jiangsu eight huge pharmaceutical Co., Ltd
<120> preparation method of imatamine
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 720
<212> DNA
<213> Nitroreductases (Burkholderia palladis)
<400> 1
tcaagcgaag aagcgggcga actcggcgac cggcgcgcgc tcggtgacga gacggttctc 60
gatcgcggcg gggtccgcat ggccgagcga catgccgcag acgagctgtt cgttggcggg 120
aatgccgagg tgttcggcga cgatccggtg aaacggcacg aatgccgcct gcgggcacgt 180
gtcgagcccg cgtgcgcggg cggccgtcat cacgccctgc aggaacatgc cgcaatcgag 240
ccatgcgccg tgggtcatga tgcgctcgag cgtgaagaac agcgcgacgg gggcgtcgaa 300
gaaacggaag ttgcgcgcgt gctgcgcgtg catgcgggct ttctcgtcgc gggcgatgtt 360
caacaggccg tacaggtccc agccgacctt gcggcgccgc tcgagatacg gcgacaccca 420
ttcgcgcggg tagtagtcgt actcggcgac gtatttctcg tcgcgggcgg gatcgtcgtg 480
agccgcggtg agcgcggcgg cgagcgcatc gcgcgtggcg cccgtcgcga cgtacacgcg 540
ccacggctgg atgttggtgc ccgacggcgc gcggctggcg gcttcgagga tcgcctcgag 600
cgtgtcgcgc gacaccggcg tgggcaggaa cgcgcggatc gcgcggcgcg acgtgagcgc 660
ggtgtcgacg gcgtcgatcg catcggcgtc gatgcgcggg gaagcggcgg gaacggacat 720
Claims (8)
1. A method for preparing imatamine, comprising the steps of:
converting the compound N- (2-methyl-5-nitrophenyl) -4- (3-pyridyl) -2-pyrimidinamine shown in the formula II into the compound imatamine shown in the formula I through an enzymatic reaction under the action of catalytic amount of nitroreductase and coenzyme;
the nitroreductase is shown by SEQ ID NO1.
2. The method for preparing immamine according to claim 1, wherein the reaction is carried out in a mixed solvent of water and an alcohol solvent.
3. Process for the preparation of immamine according to claim 2, characterized in that said alcoholic solvent is selected from methanol or ethanol.
4. Process for the preparation of immam according to claim 1, 2 or 3, characterized in that the coenzyme is a catalase.
5. Process for the preparation of immamine according to claim 4, wherein said catalase is selected from NAD+Or NADP+。
6. Process for the preparation of immam according to claim 1, 2 or 3, characterized in that the temperature of the enzymatic reaction is comprised between 30 ℃ and 40 ℃.
7. The method for preparing immam according to claim 2 or 3, wherein the mass ratio of the alcohol solvent to the water is 1: 4.0-6.0.
8. Process for the preparation of immamine according to claim 1, 2 or 3, wherein said nitroreductase is used in an amount comprised between 3% and 5% of the amount of compound of formula II.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011248048.6A CN112359079B (en) | 2020-11-10 | 2020-11-10 | Preparation method of imatamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011248048.6A CN112359079B (en) | 2020-11-10 | 2020-11-10 | Preparation method of imatamine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112359079A true CN112359079A (en) | 2021-02-12 |
| CN112359079B CN112359079B (en) | 2022-07-26 |
Family
ID=74509205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011248048.6A Active CN112359079B (en) | 2020-11-10 | 2020-11-10 | Preparation method of imatamine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112359079B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115010700A (en) * | 2022-07-19 | 2022-09-06 | 安徽海康药业有限责任公司 | Imamine preparation method based on fixed bed catalytic process |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5633158A (en) * | 1991-10-23 | 1997-05-27 | Cancer Research Campaign Technology Limited | Bacterial nitroreductase for the reduction of CB 1954 and analogues thereof to a cytotoxic form |
| US5777190A (en) * | 1997-05-29 | 1998-07-07 | Battelle Memorial Institute | Method of controlled reduction of nitroaromatics by enzymatic reaction with oxygen sensitive nitroreductase enzymes |
| US20040005676A1 (en) * | 2002-01-23 | 2004-01-08 | Diversa Corporation | Biocatalytic reduction of nitro groups |
| US20080275055A1 (en) * | 2007-05-02 | 2008-11-06 | Chemagis Ltd. | Imatinib production process |
| CN102485719A (en) * | 2011-10-09 | 2012-06-06 | 连云港盛和生物科技有限公司 | Preparation method of Imatinib amine |
| CN103242116A (en) * | 2012-02-10 | 2013-08-14 | 淮海工学院 | Novel method for preparing arylamine through reducing aromatic nitro compound |
| CN105399724A (en) * | 2015-11-05 | 2016-03-16 | 齐鲁天和惠世制药有限公司 | Preparation method of non-acicular alpha crystal form imatinib mesylate |
| CN105693690A (en) * | 2014-11-27 | 2016-06-22 | 无锡好芳德药业有限公司 | New method for preparing imatinib intermediate |
| CN105732564A (en) * | 2016-01-26 | 2016-07-06 | 济南大学 | Two-photon fluorescence probe and application thereof in detecting anoxic-zone nitroreductase |
| CN105859682A (en) * | 2015-01-18 | 2016-08-17 | 杨俊� | Synthetic method of imatinib mesylate |
| CN111039921A (en) * | 2019-12-17 | 2020-04-21 | 杭州沧海帆医药科技有限公司 | Synthesis process of imatinib and imatinib mesylate |
| WO2020131574A1 (en) * | 2018-12-18 | 2020-06-25 | Amgen Inc. | Method of reducing aromatic nitro compounds |
-
2020
- 2020-11-10 CN CN202011248048.6A patent/CN112359079B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5633158A (en) * | 1991-10-23 | 1997-05-27 | Cancer Research Campaign Technology Limited | Bacterial nitroreductase for the reduction of CB 1954 and analogues thereof to a cytotoxic form |
| US5777190A (en) * | 1997-05-29 | 1998-07-07 | Battelle Memorial Institute | Method of controlled reduction of nitroaromatics by enzymatic reaction with oxygen sensitive nitroreductase enzymes |
| US20040005676A1 (en) * | 2002-01-23 | 2004-01-08 | Diversa Corporation | Biocatalytic reduction of nitro groups |
| US20080275055A1 (en) * | 2007-05-02 | 2008-11-06 | Chemagis Ltd. | Imatinib production process |
| CN102485719A (en) * | 2011-10-09 | 2012-06-06 | 连云港盛和生物科技有限公司 | Preparation method of Imatinib amine |
| CN103242116A (en) * | 2012-02-10 | 2013-08-14 | 淮海工学院 | Novel method for preparing arylamine through reducing aromatic nitro compound |
| CN105693690A (en) * | 2014-11-27 | 2016-06-22 | 无锡好芳德药业有限公司 | New method for preparing imatinib intermediate |
| CN105859682A (en) * | 2015-01-18 | 2016-08-17 | 杨俊� | Synthetic method of imatinib mesylate |
| CN105399724A (en) * | 2015-11-05 | 2016-03-16 | 齐鲁天和惠世制药有限公司 | Preparation method of non-acicular alpha crystal form imatinib mesylate |
| CN105732564A (en) * | 2016-01-26 | 2016-07-06 | 济南大学 | Two-photon fluorescence probe and application thereof in detecting anoxic-zone nitroreductase |
| WO2020131574A1 (en) * | 2018-12-18 | 2020-06-25 | Amgen Inc. | Method of reducing aromatic nitro compounds |
| CN111039921A (en) * | 2019-12-17 | 2020-04-21 | 杭州沧海帆医药科技有限公司 | Synthesis process of imatinib and imatinib mesylate |
Non-Patent Citations (2)
| Title |
|---|
| ANDREY S. IVANOV ET AL: "Synthesis of imatinib: a convergent approach revisited", 《MONATSH CHEM》 * |
| DEPOORTER,E: "VWB83523.1", 《GENBANK》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115010700A (en) * | 2022-07-19 | 2022-09-06 | 安徽海康药业有限责任公司 | Imamine preparation method based on fixed bed catalytic process |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112359079B (en) | 2022-07-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112359079B (en) | Preparation method of imatamine | |
| CN113087609B (en) | Synthesis method of 5-chloro-1-indanone | |
| CN1106793A (en) | Preparation process of acrylamide | |
| CN110511117B (en) | Method for synthesizing 4-n-butylresorcinol by microchannel reaction | |
| CN112575044B (en) | Method for preparing key intermediate of CDK4/6 inhibitor by chemical-enzymatic method | |
| CN115232107A (en) | Preparation method of high-purity Voranolan fumarate | |
| CN112322676B (en) | Method for preparing fluvastatin by enzyme catalysis | |
| CN108147988B (en) | Preparation method of lactam compound with high chiral purity | |
| CN113735716A (en) | Preparation method of spermidine | |
| CN110092726B (en) | Synthesis method of Bictegravir intermediate | |
| CN109811019B (en) | Method for preparing droxidopa | |
| US20210380555A1 (en) | Process for preparing 6-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)nicotinamide | |
| CN112552283A (en) | Preparation method of novel tinib medicine | |
| CN113717996B (en) | Biosynthesis method of 2-deoxy-2, 2-difluoro-3, 5-dibenzoyl-D-ribofuranose | |
| CN111662182A (en) | Method for producing phenylenediamine by dinitrobenzene solvent-free hydrogenation continuous reaction | |
| JP2021113158A (en) | Method for Producing Cyclic Urea Compound | |
| CN102153460B (en) | Method for preparing glycollic acid by glycol | |
| CN115010700A (en) | Imamine preparation method based on fixed bed catalytic process | |
| CN112624901B (en) | Method for refining chiral alcohol | |
| CN111518007B (en) | Synthesis method of (S) -3-pyrrolidinol hydrochloride | |
| CN115385774B (en) | Preparation method of di-secondary aromatic alcohol | |
| CN115215877B (en) | Preparation method of Annarazole | |
| CN115286504B (en) | Method for synthesizing (R) -2- (2- (tert-butoxy) -2-oxyethyl) pentanoic acid | |
| CN112457170B (en) | Preparation method of 2,2,4, 4-tetramethyl-1, 3-cyclobutanediol | |
| CN112939994B (en) | Method for carrying out reaction of isatin compound and cyclopropenone compound under low catalytic amount |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of imamide Granted publication date: 20220726 Pledgee: Jiangsu Binhai Rural Commercial Bank Co.,Ltd. Pledgor: JIANGSU BAJU PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980005958 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |