CN111269248A - Novel method for recovering nucleoside phosphoramidate medicine mother liquor - Google Patents
Novel method for recovering nucleoside phosphoramidate medicine mother liquor Download PDFInfo
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- CN111269248A CN111269248A CN202010149526.1A CN202010149526A CN111269248A CN 111269248 A CN111269248 A CN 111269248A CN 202010149526 A CN202010149526 A CN 202010149526A CN 111269248 A CN111269248 A CN 111269248A
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- mother liquor
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- nucleoside
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- 239000012452 mother liquor Substances 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 29
- -1 nucleoside phosphoramidate Chemical class 0.000 title claims abstract description 29
- 239000002777 nucleoside Substances 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 20
- 239000012074 organic phase Substances 0.000 claims abstract description 23
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims abstract description 14
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 14
- 229960003767 alanine Drugs 0.000 claims abstract description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 12
- 239000012445 acidic reagent Substances 0.000 claims abstract description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 10
- 239000012071 phase Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000004821 distillation Methods 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 15
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 11
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 abstract description 10
- 239000011259 mixed solution Substances 0.000 abstract description 5
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 abstract description 3
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 abstract 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 abstract 1
- 238000004064 recycling Methods 0.000 abstract 1
- 238000011084 recovery Methods 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
- C07C37/0555—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group being esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/72—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/74—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by distillation
Abstract
The invention relates to a novel method for recovering nucleoside phosphoramidate medicine mother liquor, belonging to the field of chemical synthesis. The nucleoside phosphoramidate medicine mother liquor is subjected to hydrolysis reaction in the presence of an alkaline reagent, and then is kept stand for layering to respectively obtain an organic phase and a water phase; concentrating the obtained organic phase under reduced pressure, recovering the pyrazine compound, adding an acidic reagent into the aqueous phase to react to obtain a mixed solution containing pentafluorophenol, phenol and L-alanine, extracting the mixed solution by using an organic solvent, and finally recovering the pentafluorophenol, the phenol and the L-alanine by adopting a distillation mode; the scheme has great significance for recycling the mother liquor in industry.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to a novel method for recovering nucleoside phosphoramidate medicine mother liquor.
Background
At present, the related reports are few, and the yield of the reaction is low. Therefore, the invention of a mother liquor recovery method to improve the utilization rate of raw materials is very important. The mother liquor recovery method in the prior art comprises the following steps:
the yield of the product in the preparation process is low. The drug is mainly prepared by the method at present, the mother liquor contains a large amount of unextracted nucleoside phosphoramidate drugs, unreacted compounds I, unreacted compounds II and by-products pentafluorophenol, and the substances can be recycled. Therefore, the recovery and utilization of the mother liquor are of great significance in industry.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a novel method for recovering nucleoside phosphoramidate medicine mother liquor.
Nucleoside phosphoramidate drugs are prepared by the following reaction scheme:
the purpose of the invention can be realized by the following technical scheme:
a new method for recovering nucleoside phosphoramidate medicine mother liquor comprises a compound I, a compound II, a compound III and a compound IV, and the structural formula is as follows:
the compound I reacts with the compound II to synthesize a compound III and a byproduct compound IV, and the recovery method of the mother liquor comprises the following steps:
firstly, carrying out hydrolysis reaction on nucleoside phosphoramidate drug mother liquor in the presence of an alkaline reagent, standing and layering after the hydrolysis reaction is finished, and respectively obtaining an organic phase and a water phase.
Secondly, concentrating the obtained organic phase under reduced pressure, and recovering a compound I;
and thirdly, adding an acidic reagent into the water phase to react to obtain a mixed solution containing the compound IV, the phenol and the L-alanine, extracting the mixed solution for 1-5 times by using an organic solvent, and respectively recovering the compound IV, the phenol and the L-alanine from the organic phase obtained after extraction by adopting a distillation mode.
In the first step of the technical scheme of the invention, a solvent for hydrolysis reaction is selected from any one of dichloromethane, toluene and isopropyl ether, and the alkaline reagent is sodium hydroxide with the mass concentration of 15-30%, sodium carbonate with the mass concentration of 15-30% or potassium hydroxide with the mass concentration of 15-30%.
In the first step of the technical scheme of the invention, the mass ratio of the nucleoside phosphoramidate medicine mother liquor to the alkaline reagent is 1: 0.5-5, preferably the mass ratio of the nucleoside phosphoramidate medicine mother liquor to the alkaline reagent is 1: 1.5-2.5.
In the first step of the technical scheme of the invention, the temperature of hydrolysis reaction is 0-60 ℃; the hydrolysis reaction temperature is preferably 20-40 ℃.
In the third step of the technical scheme of the invention, the acidic reagent is any one or more of hydrochloric acid, sulfuric acid and acetic acid. Adding an acid reagent, and reacting at 0-60 ℃; the reaction temperature is preferably 20 to 40 ℃.
In the third step of the technical scheme of the invention, an acidic reagent is added into the water phase to adjust the pH value to 3-4.
In the third step of the technical scheme of the invention, the organic solvent used for extraction is selected from any one of dichloromethane, toluene, isopropyl ether and ethyl acetate. The distillation mode is vacuum distillation.
The reaction process of the technical scheme of the invention has the following reaction principle:
the first step is as follows: after addition of the alkaline reagent, the following reactions of the compounds occur:
compound I, which is not reacted with a basic reagent, is dissolved in the organic phase.
The products formed after the reaction of the compound II and the alkaline reagent exist in the water phase in the form of organic metal salts.
Reacting compound III with a basic agent to form compound I and an organometallic salt, wherein compound I is present in the organic phase and the organometallic salt is present in the aqueous phase.
The compound IV is reacted with a basic agent, the resulting product being present in the aqueous phase in the form of an organometallic salt.
In summary, after the addition of the alkaline reagent, the remaining product was dissolved in the aqueous phase except for the compound I in the organic phase, and the compound I was recovered by standing for liquid separation and concentrating the organic phase under reduced pressure.
And step three, adding an acidic reagent into the water phase to dissociate the organic metal salt, and respectively recovering the compound IV, the phenol and the L-alanine by extraction and reduced pressure distillation.
The general reaction route of the compound II and the compound III is as follows:
the invention has the beneficial effects that:
the invention can recycle the mother liquor of the nucleoside phosphoramidate medicine, has simple production process, higher yield, almost no pollution to the environment and easy industrial production.
The specific implementation mode is as follows:
the following detailed explanation is provided in conjunction with specific examples, which are only used to explain the technical solutions of the present invention, but the scope of the present invention is not limited thereto:
the compound IV is recovered by collecting fractions at 65-70 ℃ under the condition that the vacuum degree is 0.085 MPa: the condition for recovering the phenol is to collect the fraction at 100-105 ℃ under the condition that the vacuum degree is 0.085 MPa; the condition for recovering the L-alanine is that the fraction with the temperature of 135-140 ℃ is collected under the condition that the vacuum degree is 0.085 MPa.
The mother liquors of examples 1-3 were derived from the following reactions:
completely reacting the compound I (0.1mmol) and the compound II (0.12mmol), and separating and purifying to obtain 0.06mol of compound III. The remaining mixed solution was concentrated to obtain a mother liquor.
In examples 1 to 3, the recovery rates of the respective substances were calculated as follows:
the recovery of compound IV was: n (recovered compound IV)/n (compound II) × 100%;
the recovery rate of phenol was: n (recovered phenol)/{ n (compound III) } 100%;
the recovery rate of L-alanine was: n (recovered L-alanine)/{ n (compound ii) -n (compound III) } 100%.
In the examples of the present invention, n (compound I) is the number of moles of the starting compound I added, n (compound II) is the number of moles of the starting compound II added, and n (compound III) is the number of moles of the compound III obtained by the reaction. n (recovered compound I), n (recovered compound IV), n (recovered phenol) and n (recovered L-alanine) are the molar numbers of the recovered compound I, compound IV, phenol and L-alanine in sequence.
Example 1
The mother liquor (50g) was dissolved in methylene chloride (500ml), and 20% sodium hydroxide solution (100g) was added dropwise thereto, followed by stirring at 20 ℃ for 5 hours. TLC plate, complete hydrolysis was complete. Standing and separating to obtain an aqueous phase and an organic phase respectively. The obtained organic phase is dried by anhydrous sodium sulfate, filtered, and the filtrate is decompressed and concentrated to obtain 0.037mol of the compound I with the recovery rate of 93 percent. The pH of the resulting aqueous phase was adjusted to 3 to 4 at 20 ℃ with 1N hydrochloric acid, dichloromethane (100ml × 3) was extracted after the reaction was completed, the organic phases were combined, the organic phase was dried over anhydrous sodium sulfate, suction filtration was performed, the filtrate was distilled under reduced pressure, and then compound iv0.109mol, phenol 0.052mol, and L-alanine 0.056mol were sequentially recovered, with recovery rates of 91%, 87%, and 93%, respectively.
Example 2
The mother liquor (50g) was dissolved in toluene (500ml), and 20% sodium carbonate solution (100g) was added dropwise thereto, followed by stirring at 30 ℃ for 5 hours. TLC plates, nucleoside phosphoramidate drug and compound II were completely hydrolyzed. Standing and separating to obtain an aqueous phase and an organic phase respectively. The obtained organic phase is dried by anhydrous sodium sulfate, filtered, and the filtrate is decompressed and concentrated to obtain 0.038mol of the compound I with the recovery rate of 95%. The pH of the resulting aqueous phase was adjusted to 3 to 4 with 1N sulfuric acid at 30 ℃, the reaction solution was extracted with toluene (100ml × 3), the organic phases were combined, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was distilled under reduced pressure to recover 0.1mol of compound IV, 0.053mol of phenol, and 0.055mol of L-alanine, which were 89%, 88%, and 93%, respectively.
Example 3
The mother liquor (50g) was dissolved in isopropyl ether (500ml), and 20% potassium hydroxide solution (100g) was added dropwise thereto, followed by stirring at 40 ℃ for 5 hours. TLC plates, nucleoside phosphoramidate drug and compound II were completely hydrolyzed. Standing and separating to obtain an aqueous phase and an organic phase respectively. The obtained organic phase is dried by anhydrous sodium sulfate, filtered, and the filtrate is decompressed and concentrated to obtain 0.037mol of the compound I with the recovery rate of 92%. The resulting aqueous phase was adjusted to pH 3-4 with 10% acetic acid at 40 ℃, the reaction solution was extracted with isopropyl ether (100ml × 3), the organic phases were combined, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was distilled under reduced pressure to recover 0.108mol of compound IV, 0.053mol of phenol, and 0.053mol of L-alanine, in that order, with recovery rates of 90%, 85%, and 88%, respectively.
The above-mentioned embodiments are merely preferred embodiments of the present invention, and should not be construed as limiting the present invention, and the scope of the present invention should be defined by the claims, and equivalents including technical features of the claims, i.e., equivalent modifications within the scope of the present invention.
Claims (10)
1. A novel method for recovering nucleoside phosphoramidate medicine mother liquor is characterized by comprising the following steps:
firstly, carrying out hydrolysis reaction on nucleoside phosphoramidate medicine mother liquor in the presence of an alkaline reagent, and then standing and layering to obtain an organic phase and a water phase;
secondly, concentrating the organic phase under reduced pressure, and recovering the compound shown as the formula I;
thirdly, adding an acidic reagent into the water phase, mixing, extracting and distilling by using an organic solvent, and recovering phenol, L-alanine and a compound shown in a formula IV;
2. the method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the first step, the solvent for hydrolysis reaction is any one of dichloromethane, toluene and isopropyl ether.
3. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the first step, the alkaline reagent is sodium hydroxide with the mass concentration of 15-30%, sodium carbonate with the mass concentration of 15-30% or potassium hydroxide with the mass concentration of 15-30%.
4. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the first step, the mass ratio of the nucleoside phosphoramidate medicine mother liquor to the alkaline reagent is 1: 0.5-5.
5. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the first step, the temperature of the hydrolysis reaction is 0-60 ℃.
6. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the third step, the acidic reagent is any one or more of hydrochloric acid, sulfuric acid and acetic acid.
7. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the third step, adding an acidic reagent, and adjusting the pH value of the water phase to 3-4; the temperature for adding the acid reagent for reaction is 0-60 ℃.
8. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the third step, the organic solvent is any one of dichloromethane, toluene, isopropyl ether or ethyl acetate.
9. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: in the third step, the distillation mode is vacuum distillation.
10. The method for recovering the mother liquor of nucleoside phosphoramidates drug according to claim 1, wherein: the mother liquor of nucleoside phosphoramidate medicine contains a compound I, a compound II, a compound III and a compound IV, and the structural formula is as follows:
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| CN202010149526.1A CN111269248A (en) | 2020-03-05 | 2020-03-05 | Novel method for recovering nucleoside phosphoramidate medicine mother liquor |
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| CN202010149526.1A CN111269248A (en) | 2020-03-05 | 2020-03-05 | Novel method for recovering nucleoside phosphoramidate medicine mother liquor |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102015714A (en) * | 2008-04-23 | 2011-04-13 | 吉里德科学公司 | 1' -substituted CARBA-nucleoside analogs for antiviral treatment |
| CN104829668A (en) * | 2015-05-19 | 2015-08-12 | 江苏福瑞生物医药有限公司 | New method for recovering nucleoside phosphoramidate medicine mother liquor |
| CN107073005A (en) * | 2014-10-29 | 2017-08-18 | 吉利德科学公司 | The method for treating the infection of filamentous virus coe virus |
| WO2017184668A1 (en) * | 2016-04-20 | 2017-10-26 | Gilead Sciences, Inc. | Methods for treating flaviviridae virus infections |
| CN108348526A (en) * | 2015-09-16 | 2018-07-31 | 吉利德科学公司 | The method for treating Arenaviridae and coronaviridae virus infection |
-
2020
- 2020-03-05 CN CN202010149526.1A patent/CN111269248A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102015714A (en) * | 2008-04-23 | 2011-04-13 | 吉里德科学公司 | 1' -substituted CARBA-nucleoside analogs for antiviral treatment |
| CN107073005A (en) * | 2014-10-29 | 2017-08-18 | 吉利德科学公司 | The method for treating the infection of filamentous virus coe virus |
| CN104829668A (en) * | 2015-05-19 | 2015-08-12 | 江苏福瑞生物医药有限公司 | New method for recovering nucleoside phosphoramidate medicine mother liquor |
| CN108348526A (en) * | 2015-09-16 | 2018-07-31 | 吉利德科学公司 | The method for treating Arenaviridae and coronaviridae virus infection |
| WO2017184668A1 (en) * | 2016-04-20 | 2017-10-26 | Gilead Sciences, Inc. | Methods for treating flaviviridae virus infections |
Non-Patent Citations (1)
| Title |
|---|
| DUSTIN SIEGEL ET AL.: ""Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f ][triazin-4-amino] Adenine C‑Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses"", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
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Application publication date: 20200612 |