CN112500321A - Preparation method of feloxicib key intermediate - Google Patents
Preparation method of feloxicib key intermediate Download PDFInfo
- Publication number
- CN112500321A CN112500321A CN202011019923.3A CN202011019923A CN112500321A CN 112500321 A CN112500321 A CN 112500321A CN 202011019923 A CN202011019923 A CN 202011019923A CN 112500321 A CN112500321 A CN 112500321A
- Authority
- CN
- China
- Prior art keywords
- organic solvent
- isobutyrylphenyl
- boric acid
- reaction
- boron
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 23
- 150000001638 boron Chemical class 0.000 claims abstract description 13
- CUSYFGJMAUMHCQ-UHFFFAOYSA-N C(C(C)C)(=O)C1=CC=C(C=C1)OB(O)O Chemical compound C(C(C)C)(=O)C1=CC=C(C=C1)OB(O)O CUSYFGJMAUMHCQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000003651 drinking water Substances 0.000 claims description 6
- 235000020188 drinking water Nutrition 0.000 claims description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 150000001879 copper Chemical class 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 2
- ZKXWKVVCCTZOLD-FDGPNNRMSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O ZKXWKVVCCTZOLD-FDGPNNRMSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 150000003568 thioethers Chemical class 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 6
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 5
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- CFUNNCDOCRSHJT-UHFFFAOYSA-N [4-(2-methylpropanoyl)phenyl]boronic acid Chemical compound CC(C)C(=O)C1=CC=C(B(O)O)C=C1 CFUNNCDOCRSHJT-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 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 description 2
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KMWUDQCOBHVOGJ-UHFFFAOYSA-N 2-cyclopropyloxyacetic acid Chemical compound OC(=O)COC1CC1 KMWUDQCOBHVOGJ-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 1
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- HCMUPMCWKYOOBZ-UHFFFAOYSA-N methyl 2-(4-methylsulfonylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(S(C)(=O)=O)C=C1 HCMUPMCWKYOOBZ-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- QLVDOWBJYVLGIP-UHFFFAOYSA-M sodium;methyl sulfite Chemical compound [Na+].COS([O-])=O QLVDOWBJYVLGIP-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000013389 whole blood assay Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of a key intermediate of felicoxib, and relates to the technical field of chemical synthesis methods. The method adopts (4-isobutyrylphenyl) boric acid or boron derivatives as raw materials, and obtains the key intermediate of the feloxicib directly through one-step reaction. Compared with the traditional process, the method avoids using thioether intermediate state, is more environment-friendly, has simple post-treatment process, does not need column chromatography to separate the intermediate state and the product, has high yield and low cost, and is suitable for industrial production.
Description
One, the technical field
The present invention relates to a method of chemical synthesis, in particular a novel method of synthesis of key intermediates of felicoxib avoiding the use of thioethers (as starting materials or intermediates).
Second, background Art
The feloxicib is a non-steroidal anti-inflammatory drug for animals, and can play a role in antipyresis, analgesia and anti-inflammation through selectively inhibiting cyclooxygenase-2 (COX-2) mediated prostaglandin synthesis. COX-2 is a subtype of cyclooxygenase and is primarily responsible for the synthesis of prostaglandins, regulating pain, inflammation and fever. Selective inhibition of COX-2 is effective in alleviating osteoarthritis pain. In a whole blood assay in vitro in dogs, feloxib was approximately 380 times selective for COX-2 over COX-1. Approved by the FDA, feloxicib is currently used to treat equine osteoarthritis as well as acute and chronic pain and inflammation resulting from clinical surgery. The product has good treatment effect and palatability, and has good market prospect.
At present, few reports about the synthesis of the felicoxib exist, and the synthetic method of the felicoxib disclosed in the patent WO9714691 mainly uses the methyl phenyl sulfide as a raw material to prepare the felicoxib through an F-C acylation reaction, an oxidation reaction, a bromination reaction and a cyclopropoxy acetic acid reaction in sequence.
The synthesis by the above method inevitably requires the use of thioether (as a starting material or an intermediate), which has the disadvantages of easy volatilization and heavy odor, and a series of studies have been made to avoid the use of thioether (as a starting material or an intermediate), including:
CN110452199 uses the following method: directly using the oxidized p-methyl sulfonyl phenylacetic acid methyl ester as a starting material;
the following general methods were used in CN110105314, CN107686471 and CN 111201212:
CN107778204 uses the following general formula:
third, the invention
The invention aims to provide a preparation method of a key intermediate of feloxib, which has less pollution and mild reaction conditions.
The structural formula of the prepared feloxicib intermediate is as follows, namely, the compound (2-methyl-1- [4- (methylsulfonyl) phenyl ] -1-acetone) in the formula I;
in view of the variety of commercially available or readily available boronic acids and borates, and the compatibility of these compounds with a wide range of functional groups, we consider these boron derivatives as precursors in the preparation of sulfones.
In order to realize the purpose, the preparation method of the feloxicib intermediate adopts the technical scheme that:
a preparation method of a key intermediate of feloxicib comprises the following steps:
(1) adding (4-isobutyrylphenyl) boric acid or boron derivatives, sodium methanesulfinate, a catalyst and an alkali into an organic solvent, heating the system to 40-190 ℃, and reacting for 5-20 h to obtain a reaction solution.
(2) Adding a proper amount of drinking water into the reaction liquid, adding a proper amount of organic solvent for multiple times of extraction, merging organic phases, and evaporating the organic solvent under reduced pressure to obtain the intermediate, namely the compound (2-methyl-1- [4- (methylsulfonyl) phenyl ] -1-acetone) of the formula I.
In a further aspect of the above-described method of preparation,
wherein the catalyst in the step (1) is CuI or CuBr2、Cu(NO3)2、Cu(acac)2、Cu(OAc)2、Cu(TFA)2More preferably Cu (OAc)2；
The base in the step (1) is one or more of triethylamine, potassium carbonate, sodium carbonate, pyridine and DBU, and potassium carbonate is further preferable.
The organic solvent in the step (1) is one or more of dimethyl sulfoxide, N-dimethylformamide, tetrahydrofuran, isopropanol and dichloromethane, and is further preferably dimethyl sulfoxide;
the amount of the copper salt as the catalyst used in the step (1) is 0.001 to 1.5 equivalents, and more preferably 0.1 equivalent, of the (4-isobutyrylphenyl) boronic acid or boron derivative.
The amount of the base used in the step (1) is 1.5 to 5.0 equivalents, and more preferably 2.0 equivalents, of the (4-isobutyrylphenyl) boronic acid or boron derivative.
The volume consumption of the organic solvent in the step (1) is 5-20 times, and more preferably 10 times of the mass of the (4-isobutyrylphenyl) boric acid or boron derivative.
In the step (1), the reaction temperature is 40-190 ℃, the reaction time is 5-20 h, the reaction temperature is further preferably 60-120 ℃, and the reaction time is 6-10 h.
In the step (2), the amount of drinking water is 5 to 20 times, preferably 8 times, the weight of the drinking water containing (4-isobutyrylphenyl) boric acid or boron derivatives.
In the step (2), the organic solvent is one of ethyl acetate, dichloromethane, isopropyl acetate and toluene, and ethyl acetate is more preferable.
In the step (2), the temperature for removing the organic solvent by reduced pressure distillation is 35-75 ℃, and the preferable temperature is 45-55 ℃.
The technical route of the invention is as follows:
compared with the prior art, the invention has the advantages that:
1. according to the invention, the (4-isobutyrylphenyl) boric acid or boron derivative is used as a reaction raw material, so that a target product with high yield can be obtained, and the use of thioether or sulfoxide and other compound raw materials or intermediates which are harmful to the environment is avoided, so that the production is more environment-friendly;
2. the invention adopts a one-pot method to prepare the target compound, adopts one-time feeding and one-step reaction mode, has less side reaction, is convenient to control the reaction, is easy to separate the target compound, and greatly improves the quality and the yield of the product.
Fourthly, the specific implementation case is as follows:
the synthesis process of the compound of the formula I is specifically operated as follows:
(1) the compound of formula II (28.80g, 0.15mol) was dissolved in DMSO (288ml) and Cu (OAc) was added directly to it at room temperature2(3.00g, 0.015mol), potassium carbonate (41.16g, 0.30mol), sodium methylsulphite (30.63g, 0.30mol), after stirring for a few minutes after addition, the temperature was slowly raised to 60 ℃ for 12h and the starting material (compound of formula II) was monitored by HPLC for completion of the reaction.
(2) After the temperature is reduced, drinking water (230ml) is added into the reaction solution, ethyl acetate is added into the reaction solution for extraction (150ml +100ml +100ml) in three batches, the organic phases extracted for three times are combined, anhydrous sodium sulfate is added for drying for 1h, a drying agent is filtered out, and the filtrate is subjected to reduced pressure concentration at 50 ℃ until the solvent is dried, so that the compound of the formula I (30.21g, 0.13mol, light yellow solid, yield: 86.7%) is obtained;1H NMR(400MHZ，CDCl3)，δ：8.26～7.94(m,4H),3.34(s，1H)，3.31(m，3H)，1.19～1.17(m，6H)。
the above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (11)
1. A preparation method of a key intermediate (a compound shown as a formula I) of feloxicib,
the method comprises the following specific steps:
(1) adding (4-isobutyrylphenyl) boric acid or boron derivatives, sodium methanesulfinate, a catalyst and an alkali into an organic solvent, heating the system to 40-190 ℃, and reacting for 5-20 h to obtain a reaction solution;
(2) adding a proper amount of drinking water into the reaction liquid, adding a proper amount of organic solvent for multiple times of extraction, merging organic phases, and evaporating the organic solvent under reduced pressure to obtain the target intermediate, namely the compound (2-methyl-1- [4- (methylsulfonyl) phenyl ] -1-acetone) shown in the formula I.
2. The method of claim 1, wherein: the catalyst in the step (1) is CuI or CuBr2、Cu(NO3)2、Cu(acac)2、Cu(OAc)2、Cu(TFA)2One or more of them.
3. The method of claim 1, wherein: and (2) in the step (1), the alkali is one or more of triethylamine, potassium carbonate, sodium carbonate, pyridine and DBU.
4. The method of claim 1, wherein: the organic solvent in the step (1) is one or more of dimethyl sulfoxide, N-dimethylformamide, tetrahydrofuran, isopropanol and dichloromethane.
5. The method of claim 1, wherein: the dosage of the copper salt used as the catalyst in the step (1) is 0.001-1.5 equivalent of (4-isobutyrylphenyl) boric acid or boron derivatives.
6. The method of claim 1, wherein: the amount of the alkali used in the step (1) is 1.5-5.0 equivalents of (4-isobutyrylphenyl) boric acid or boron derivatives.
7. The method of claim 1, wherein: the volume consumption of the organic solvent in the step (1) is 5-20 times of the mass of the (4-isobutyrylphenyl) boric acid or boron derivative.
8. The method of claim 1, wherein: the reaction temperature in the step (1) is 40-190 ℃, and the reaction time is 5-20 h.
9. The method of claim 1, wherein: in the step (2), a proper amount of drinking water is 5-20 times of the mass of the (4-isobutyrylphenyl) boric acid or the boron derivative.
10. The method of claim 1, wherein: in the step (2), the organic solvent is one of ethyl acetate, dichloromethane, isopropyl acetate and toluene.
11. The method of claim 1, wherein: in the step (2), the temperature for removing the organic solvent by reduced pressure evaporation is 35-75 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011019923.3A CN112500321A (en) | 2020-09-25 | 2020-09-25 | Preparation method of feloxicib key intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011019923.3A CN112500321A (en) | 2020-09-25 | 2020-09-25 | Preparation method of feloxicib key intermediate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112500321A true CN112500321A (en) | 2021-03-16 |
Family
ID=74953688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011019923.3A Pending CN112500321A (en) | 2020-09-25 | 2020-09-25 | Preparation method of feloxicib key intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112500321A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102260200A (en) * | 2011-03-16 | 2011-11-30 | 清华大学 | Method for synthesizing phenylsulfone compounds |
| CN107686471A (en) * | 2017-09-28 | 2018-02-13 | 四川青木制药有限公司 | A kind of Fei Luokao former times and its synthetic method of intermediate |
| CN107778204A (en) * | 2017-10-26 | 2018-03-09 | 扬州天和药业有限公司 | A kind of preparation method of Fei Luokao former times intermediate |
| CN109053505A (en) * | 2018-08-03 | 2018-12-21 | 四川青木制药有限公司 | A kind of synthetic method of Fei Luokao former times important intermediate |
| CN110105314A (en) * | 2019-06-02 | 2019-08-09 | 江苏君若医药有限公司 | One method for preparing Fei Luokao former times |
-
2020
- 2020-09-25 CN CN202011019923.3A patent/CN112500321A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102260200A (en) * | 2011-03-16 | 2011-11-30 | 清华大学 | Method for synthesizing phenylsulfone compounds |
| CN107686471A (en) * | 2017-09-28 | 2018-02-13 | 四川青木制药有限公司 | A kind of Fei Luokao former times and its synthetic method of intermediate |
| CN111201212A (en) * | 2017-09-28 | 2020-05-26 | 四川青木制药有限公司 | Synthesis method of feloxicib and intermediate thereof |
| CN107778204A (en) * | 2017-10-26 | 2018-03-09 | 扬州天和药业有限公司 | A kind of preparation method of Fei Luokao former times intermediate |
| CN109053505A (en) * | 2018-08-03 | 2018-12-21 | 四川青木制药有限公司 | A kind of synthetic method of Fei Luokao former times important intermediate |
| CN110105314A (en) * | 2019-06-02 | 2019-08-09 | 江苏君若医药有限公司 | One method for preparing Fei Luokao former times |
Non-Patent Citations (1)
| Title |
|---|
| BEAULIEU, CHRISTIAN 等: "A mild and efficient new synthesis of aryl sulfones from boronic acids and sulfinic acid salts" * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100273888B1 (en) | 2,2-dichloroalkane carboxylic acids, process for preparing the same, medicament containing the same, and use thereof for treating insulin resistance | |
| CN111201212B (en) | Synthesis method of feloxicib and intermediate thereof | |
| JPS6330458A (en) | Acylanilide, manufacture and medicinal and veterinary composition having progesterone-like activity | |
| MX2014003894A (en) | Production method for 4, 4-difluoro-3,4-dihydroisoquinoline derivative. | |
| CZ436898A3 (en) | Process for preparing phenylheterocyclic derivatives | |
| IL46027A (en) | Organo-metallic compounds their preparation and pharmaceutical compositions containing them | |
| WO2023019839A1 (en) | Preparation and post-treatment method for 5-aminolevulinate | |
| CN112500321A (en) | Preparation method of feloxicib key intermediate | |
| CN105693632B (en) | A kind of preparation method of polysubstituted quinoxaline derivant | |
| CN107445869A (en) | A kind of synthetic method of Metformin hydrochloride | |
| WO2009127116A1 (en) | 13-halo-3,15-dioxy gibberellic acid esters and the preparation methods thereof | |
| CN103450092B (en) | Synthesis method of metronidazole-sulfanilamide derivatives | |
| KR870000205B1 (en) | Process for preparing phenoxy alkanedione derivatives | |
| WO2017152539A1 (en) | 4-sulfur pentafluoride phenol compound and preparation method therefor, and preparation method for sulfur pentafluoride substituted benzopyran compound | |
| CN107936045A (en) | A kind of preparation method of high-purity Flurbiprofen known impurities | |
| CN109761868B (en) | Synthesis method of optically pure chlorprostenol | |
| CN109232316B (en) | Synthetic method of alpha-tertiary nitrile structure beta-dicarbonyl compound | |
| CN108822072B (en) | Method for preparing Elligusurgitol | |
| US3450698A (en) | Phenthiazine derivatives | |
| CN105111217B (en) | A kind of synthetic method of iso-indoles dihydroquinazoline derivatives | |
| CN105153050A (en) | Quinocetone derivative and preparation method thereof | |
| JPS6245553A (en) | Production of phenylacetic acid derivative | |
| WO2011082623A1 (en) | Method for preparing febuxostat | |
| CN112624936A (en) | Aqueous phase synthesis method of tolfenamic acid | |
| CN115504905A (en) | Gelmethine intermediate compound |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210316 |
|
| RJ01 | Rejection of invention patent application after publication |