CN107827938B - Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose - Google Patents
Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose Download PDFInfo
- Publication number
- CN107827938B CN107827938B CN201711038155.4A CN201711038155A CN107827938B CN 107827938 B CN107827938 B CN 107827938B CN 201711038155 A CN201711038155 A CN 201711038155A CN 107827938 B CN107827938 B CN 107827938B
- Authority
- CN
- China
- Prior art keywords
- deoxy
- tri
- acetyl
- ribose
- compound
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention discloses a preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose, belonging to the field of nucleoside drug synthesis, which comprises the following reaction steps of reacting inosine as a raw material with organic boric acid to protect 2 'and 3' hydroxyls, then reducing at room temperature under the conditions of potassium borohydride and trifluoroacetic acid, then carrying out glycol exchange deprotection, and finally adding acetic anhydride for reflux reaction to obtain the 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose.
Description
Technical Field
The invention belongs to the field of nucleoside drug synthesis, and particularly relates to a preparation method of a capecitabine key intermediate 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose.
Background
1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose, CAS: 62211-93-2, mainly used in the synthesis of Capecitabine (Capecitabine). Capecitabine is a novel antitumor drug developed by Roche and approved by the FDA in 1998 to be marketed in the United states under the trade name XE L ODA (Hiroda).
The published data show that the process route of capecitabine is more reported, and a representative patent WO2009071726A1 discloses a synthesis method of capecitabine, which adopts 5-fluorocytosine as a starting material, introduces a nonpolar side chain by acylating an amino group on a pyrimidine ring, then couples the nonpolar side chain with 1,2, 3-O-triacetyl-5-deoxy- β -D-ribose, and finally removes a diacetyl group on a glycosyl group through hydrolysis to obtain the capecitabine.
At present, the literature reports about the synthetic route of 1,2, 3-O-triacetyl-5-deoxy- β -D-ribose, and the following main synthetic routes are reported:
US4340729 uses D-ribose as the starting material, and converts it into 5-deoxy-D-ribose, and then triacetylates it to prepare the target product, which is a simple and common method, but has the disadvantages of long synthesis route, oily intermediates, difficult purification, low total yield, especially the final step of the triacetylation of 5-deoxy-D-ribose, low proportion of β/α at position 1, resulting in total yield of 25-30%, and no competitive advantage in industrial production.
CN100432088 adopts inosine as a starting material, and prepares 1,2, 3-O-triacetyl-5-deoxy- β -D-ribose through three steps of iodination, reduction, acetylation and the like, the starting material inosine of the route has lower cost than D-ribose, but the route has the disadvantages that iodine is used as an iodination reagent, the molecular utilization rate is low, more black iodine-containing wastewater is generated in the iodination and deiodination processes, the pressure of three-waste treatment is increased, a large amount of expensive triphenyl phosphorus is used in the iodination reaction, the generated triphenyl phosphorus oxide is difficult to remove, the treatment and purification after the reaction are difficult, the total yield is low, and the actual operation total yield is not more than 60%.
CN102432642B takes inosine as a starting material, is acylated by tosyl chloride to obtain 5 '-tosyl-6-hydroxy-9-D-purine nucleoside, then is reduced under the action of sodium borohydride to obtain 5' -deoxy-6-hydroxy-9- β -D-purine nucleoside, then is subjected to acylation reaction with acetic anhydride to prepare 2, 3-O-diacetyl-5-deoxyinosine, and finally is subjected to glycosidase removal and acetylation simultaneously to obtain a target product 1,2, 3-O-triacetyl-5-deoxy-D-ribofuranose.
At present, a technical scheme which has short operation steps, convenient and easily obtained raw material sources, safe and controllable operation process and industrial prospect for synthesizing the 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose still needs to be developed.
Disclosure of Invention
Inosine is used as a raw material to react with organic boric acid to protect 2 'and 3' hydroxyl, then reduction is carried out at room temperature under the conditions of potassium borohydride and trifluoroacetic acid, then diol exchange deprotection is carried out, and finally acetic anhydride is added for reflux reaction to obtain 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose.
A process for preparing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose, wherein the reaction equation is as follows:
the method comprises the following reaction steps: inosine with RB (OH)2Reacting to obtain a compound 2; followed by Compound 2 in KBH4And CF3CO2Reducing under H condition, adding diol to remove protection to obtain 3, and refluxing the compound 3 in acetic anhydride to obtain 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose.
Further, said RB (OH)2Selected from the group consisting of MeB (OH)2Or PhB (OH)2(ii) a Inosine with RB (OH)2The molar ratio of (A) to (B) is 1: 1-1.05. Using methanol, toluene, ethyl acetate or tetrahydrofuran monoDehydrating in one or mixed solvent to obtain compound 2.
Further, the compound 2, KBH4、CF3CO2The molar ratio of H is 1:0.35-0.45: 4-6. Using NaBH4In time, the reaction is relatively violent, and potential safety hazards exist.
Further, the diol is selected from pinacol or neopentyl glycol. When the protection is performed by the boric acid removal, a catalytic amount of copper acetate (0.03-0.15eq) is added to facilitate the deprotection. The reaction principle is that boric acid ester with lower boiling point and stability is generated with diol under the acidic condition, so that the protection is effectively removed.
Further, when the compound 3 reacts with acetic anhydride, inorganic boric acid is added. The inorganic boric acid plays a role in accelerating the dissociation of the glycosidic bond, and the reaction can be completed without adding the inorganic boric acid.
Further, the molar ratio of the compound 3, acetic anhydride and inorganic boric acid is 1:10-15: 0.05-0.10.
The invention has the beneficial effects that:
1. the invention is common commercial raw materials and reagents, has convenient sources, is easy for industrial production and has good application prospect.
2. In the invention, organic boric acid is adopted to protect 2-position and 3-position of glycosyl part, and diol acid exchange is adopted to generate more stable low-boiling-point organic borate for deprotection, so that the organic borate can be removed.
3. The catalyst is composed of potassium borohydride and an acid system, positive carbon ions formed by hydroxyl are immediately reduced, the operation is milder, and the safety is higher.
4. The product of each step can be directly carried out downwards without purification, and the purity of the final product can reach more than 99 percent after the final product is recrystallized by adopting an isopropanol system.
The specific embodiment is as follows:
example 1
Preparation of 2 ', 3' -methylboronic acid ester-inosine (2)
A250 m L three-necked flask with a stirrer and a thermometer was charged with inosine (20g,0.0746mol), a mixed solvent of methanol and toluene (volume ratio 1: 5, 100m L) and MeB (OH)2(4.03g,1.0eq), heating and refluxing for 3 hours, detecting by HP L C, and reactingAfter that, the solvent is distilled under normal pressure, 130m L ethanol is added to be cooled to about 10 ℃, and 20.2g of solid is obtained after suction filtration and drying, and the yield is 92.7%.
Preparation of 5' -deoxyinosine (3)
In a 250m L three-necked bottle for low-temperature reaction, 20.0g of compound 2(0.0685mol) is added with 25.45m L trifluoroacetic acid (5.0eq), the mixture is cooled to the temperature of between 10 ℃ below zero and 0 ℃, potassium borohydride (1.29g, 0.35eq) is added in batches at intervals of more than 10 minutes every time, the mixture is stirred after the addition is finished, HP L C detects that the raw material is less than 2 percent remained, methanol 65m L is added to slowly quench a reaction system, pinacol (8.1g,1.0eq) and copper acetate (0.55g,0.04eq) are added to react for 12 hours at room temperature, most of solvent is concentrated under reduced pressure, the mixture is poured into water 80m L, placed for crystallization, and subjected to suction filtration and drying to obtain 14.6g of solid with the yield of 84.54%.
Preparation of 5-deoxy-tri-O-acetyl sugar (4)
Adding 5' -deoxyinosine (20g,0.0794mol) and acetic anhydride (100 m L) into a 250m L three-necked bottle with a stirrer and a thermometer, heating and refluxing for reaction for 1 hour, adding 0.24g (0.05eq) of inorganic boric acid, continuing the reaction for 10 hours, separating out solids, cooling to 10 ℃, performing suction filtration to remove acetylhypoxanthine solids, performing reduced pressure concentration on the filtrate, adding 30m L of isopropanol once, adding 45m L of isopropanol, cooling and crystallizing to obtain 17.3g of 5-deoxy-tri-O-acetylglucose, wherein the yield is 83.7%, the purity of HP L C is 99.6%, and the purity of single impurities is 0.11%.
Example 2
Preparation of 2 ', 3' -methylboronic acid ester-inosine (2)
A250 m L three-necked flask with a stirrer and a thermometer was charged with inosine (20g,0.0746mol), a mixed solvent of methanol and ethyl acetate (volume ratio 1: 5, 100m L) and MeB (OH)2(4.03g,1.0eq), reacting at room temperature for 5 hours, detecting by HP L C to confirm the reaction is finished, distilling the solvent under normal pressure, adding 130m L ethanol, cooling to about 10 ℃, filtering and drying to obtain a solid 18.6g, wherein the yield is 85.4%.
Preparation of 5' -deoxyinosine (3)
In a 250m L three-necked bottle for low-temperature reaction, 20.0g of compound 2(0.0685mol) is added with 25.45m L trifluoroacetic acid (5.0eq), the mixture is cooled to the temperature of between 10 ℃ below zero and 0 ℃, potassium borohydride (1.66g, 0.45eq) is added in batches, the mixture is stirred for more than 10 minutes every time after the completion of the addition, HP L C detects that the raw material is less than 1.3 percent remained, methanol 65m L is added to slowly quench the reaction system, pinacol (8.1g,1.0eq) and copper acetate (0.55g,0.04eq) are added to react for 12 hours at room temperature, most of the solvent is concentrated under reduced pressure, the mixture is poured into water 80m L, placed for crystallization, and subjected to suction filtration and drying to obtain 15.1g of solid, wherein the yield is 87.43%.
Preparation of 5-deoxy-tri-O-acetyl sugar (4)
Adding 5' -deoxyinosine (20g,0.0794mol) and acetic anhydride (100 m L) into a 250m L three-necked bottle with a stirrer and a thermometer, heating and refluxing for 1 hour, adding 0.24g (0.05eq) of inorganic boric acid, continuing to react for 10 hours, separating out solids, cooling to 10 ℃, performing suction filtration to remove acetylhypoxanthine solids, performing reduced pressure concentration on the filtrate, adding 30m L of isopropanol once, adding 45m L of isopropanol, cooling and crystallizing to obtain 17.3g of 5-deoxy-tri-O-acetylglucose, wherein the yield is 83.7%, the HP L C is 99.7%, and the maximum single impurity content is 0.09%.
Example 3
Preparation of 2 ', 3' -methylboronic acid ester-inosine (2)
A250 m L three-necked flask with a stirrer and a thermometer was charged with inosine (20g,0.0746mol), a mixed solvent of methanol and toluene (volume ratio 1: 5, 100m L) and PhB (OH)2(9.09g,1.0eq), heating and refluxing for 3 hours, detecting by HP L C, distilling the solvent under normal pressure after the reaction is finished, adding 130m L ethanol, cooling to about 10 ℃, filtering and drying to obtain 21.8g of solid with the yield of 82.57 percent.
Preparation of 5' -deoxyinosine (3)
In a 250m L three-necked bottle for low-temperature reaction, 20.0g of compound 2(0.0685mol) is added into 20.35m L trifluoroacetic acid (4.0eq), the mixture is cooled to a temperature of between 10 ℃ below zero and 0 ℃, potassium borohydride (1.66g, 0.45eq) is added in batches, the mixture is stirred for more than 10 minutes every time after the completion of the addition, HP L C detects that the raw material is less than 0.15 percent remained, methanol 65m L is added to slowly quench the reaction system, pinacol (8.1g,1.0eq) and copper acetate (0.55g,0.04eq) are added to react for 12 hours at room temperature, most of the solvent is concentrated under reduced pressure, the mixture is poured into water 80m L, placed for crystallization, and subjected to suction filtration and drying to obtain 13.7g of solid, wherein the yield is 79.33%.
Preparation of 5-deoxy-tri-O-acetyl sugar (4)
Adding 5' -deoxyinosine (20g,0.0794mol) and acetic anhydride (75 m L) into a 250m L three-necked bottle with a stirrer and a thermometer, heating and refluxing for 1 hour, adding 0.24g (0.05eq) of inorganic boric acid, continuing to react for 12 hours, separating out solids, cooling to 10 ℃, performing suction filtration to remove acetylhypoxanthine solids, performing reduced pressure concentration on the filtrate, adding 30m L of isopropanol once, adding 45m L of isopropanol, cooling and crystallizing to obtain 16.2g of 5-deoxy-tri-O-acetylglucose, wherein the yield is 78.45%, and the HP L C is 99.5%.
Example 4
Preparation of 2 ', 3' -methylboronic acid ester-inosine (2)
A250 m L three-necked flask with a stirrer and a thermometer was charged with inosine (20g,0.0746mol), a mixed solvent of methanol and toluene (volume ratio 1: 5, 100m L) and MeB (OH)2(4.69g,1.05eq), heating and refluxing for 3 hours, detecting by HP L C, distilling the solvent under normal pressure after the reaction is finished, adding 130m L ethanol, cooling to about 10 ℃, filtering and drying to obtain 20.6g of solid with the yield of 94.6 percent.
Preparation of 5' -deoxyinosine (3)
In a 250m L three-necked bottle for low-temperature reaction, 20.0g of compound 2(0.0685mol) is added with 25.45m L trifluoroacetic acid (5.0eq), the mixture is cooled to the temperature of between 10 ℃ below zero and 0 ℃, potassium borohydride (1.66g, 0.45eq) is added in batches at intervals of more than 10 minutes every time, the mixture is stirred after the addition is finished, HP L C detects that the raw material is less than 2 percent remained, methanol 65m L is added to slowly quench a reaction system, pinacol (8.1g,1.0eq) and copper acetate (0.55g,0.04eq) are added to react for 12 hours at room temperature, most of solvent is concentrated under reduced pressure, the mixture is poured into water 80m L, placed for crystallization, and subjected to suction filtration and drying to obtain 15.3g of solid with the yield of 88.59%.
Preparation of 5-deoxy-tri-O-acetyl sugar (4)
Adding 5' -deoxyinosine (20g,0.0794mol) and acetic anhydride (100 m L) into a 250m L three-necked bottle with a stirrer and a thermometer, heating and refluxing for 1 hour, adding 0.49g (0.1eq) of inorganic boric acid, continuing to react for 8 hours, separating out solids, cooling to 10 ℃, performing suction filtration to remove acetylhypoxanthine solids, performing reduced pressure concentration on the filtrate, adding 30m L of isopropanol once, adding 45m L of isopropanol, cooling and crystallizing to obtain 17.9g of 5-deoxy-tri-O-acetylglucose, wherein the yield is 86.68%, the HP L C is 99.8%, and the maximum single impurity is 0.03%.
Example 5
Preparation of 2 ', 3' -methylboronic acid ester-inosine (2)
A250 m L three-necked flask with a stirrer and a thermometer was charged with inosine (20g,0.0746mol), a mixed solvent of methanol and toluene (volume ratio 1: 5, 100m L) and MeB (OH)2(4.69g,1.05eq), heating and refluxing for 3 hours, detecting by HP L C, distilling the solvent under normal pressure after the reaction is finished, adding 130m L ethanol, cooling to about 10 ℃, filtering and drying to obtain 20.6g of solid with the yield of 94.6 percent.
Preparation of 5' -deoxyinosine (3)
In a 250m L three-necked bottle for low-temperature reaction, 20.0g of compound 2(0.0685mol) is added with 25.45m L trifluoroacetic acid (5.0eq), the mixture is cooled to the temperature of between 10 ℃ below zero and 0 ℃, potassium borohydride (1.66g, 0.45eq) is added in batches at intervals of more than 10 minutes every time, the mixture is stirred after the addition is finished, HP L C detects that the raw material is less than 2 percent remained, methanol 65m L is added to slowly quench a reaction system, neopentyl glycol (7.13g,1.0eq) and copper acetate (0.55g,0.04eq) are added to react for 12 hours at room temperature, most of solvent is concentrated under reduced pressure, the mixture is poured into water 80m L, placed for crystallization, and dried by suction filtration to obtain 12.7g of solid with the yield of 73.53 percent.
Preparation of 5-deoxy-tri-O-acetyl sugar (4)
Adding 5' -deoxyinosine (20g,0.0794mol) and acetic anhydride (100 m L) into a 250m L three-necked bottle with a stirrer and a thermometer, heating and refluxing for 1 hour, adding 0.24g (0.05eq) of inorganic boric acid, continuing to react for 10 hours, separating out solids, cooling to 10 ℃, performing suction filtration to remove acetylhypoxanthine solids, performing reduced pressure concentration on the filtrate, adding 30m L of isopropanol once, adding 45m L of isopropanol, cooling and crystallizing to obtain 17.3g of 5-deoxy-tri-O-acetylglucose, wherein the yield is 83.7 percent, and the HP L C is 99.6 percent.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (6)
1. A process for preparing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose, wherein the reaction equation is as follows:
the method comprises the following reaction steps: inosine with RB (OH)2Reacting to obtain a compound 2; followed by Compound 2 in KBH4And CF3CO2Reducing under H condition, adding diol to remove protection to obtain compound 3, reflux reacting compound 3 in acetic anhydride to obtain 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose, RB (OH)2Selected from the group consisting of MeB (OH)2Or PhB (OH)2。
2. The method for producing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose according to claim 1, wherein inosine is mixed with RB (OH)2The molar ratio of (A) to (B) is 1: 1-1.05.
3. The method for preparing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose according to claim 1, wherein the compound 2 is KBH4、CF3CO2The molar ratio of H is 1:0.35-0.45: 4-6.
4. The process for preparing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose according to claim 1, wherein the diol is selected from pinacol or neopentyl glycol, and 0.03 to 0.15 equivalent of cupric acetate is added during deprotection.
5. The process for preparing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose according to claim 1, wherein an inorganic boric acid is added in the reaction of Compound 3 with acetic anhydride.
6. The process for preparing 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose according to claim 5, wherein the molar ratio of compound 3, acetic anhydride and inorganic boric acid is 1:10-15: 0.05-0.10.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711038155.4A CN107827938B (en) | 2017-10-27 | 2017-10-27 | Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711038155.4A CN107827938B (en) | 2017-10-27 | 2017-10-27 | Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107827938A CN107827938A (en) | 2018-03-23 |
| CN107827938B true CN107827938B (en) | 2020-08-07 |
Family
ID=61650868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711038155.4A Active CN107827938B (en) | 2017-10-27 | 2017-10-27 | Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107827938B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108484690B (en) * | 2018-05-16 | 2021-04-30 | 新乡拓新药业股份有限公司 | Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy-beta-D-ribose |
| CN108727440B (en) * | 2018-05-16 | 2021-12-17 | 新乡拓新药业股份有限公司 | Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy-beta-D-ribose |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101012252A (en) * | 2007-01-30 | 2007-08-08 | 王成举 | Method of synthesizing 1,2,3-tri-O-acetyl-5-deoxidation-D-ribose |
| JP2009256335A (en) * | 2008-03-26 | 2009-11-05 | Univ Of Tokyo | Preparation method of ribonucleic acid having alkyl protective group at position 2' |
| CN102432642A (en) * | 2011-10-17 | 2012-05-02 | 江西科技师范学院 | Synthesis method of 1,2,3-O-triacetyl-5-deoxy-D-ribofuranose |
| CN104650160A (en) * | 2015-01-13 | 2015-05-27 | 济南大学 | Novel synthesis method of capecitabine key intermediate 1,2,3-O-triacetyl-5-deoxy-D-ribose |
-
2017
- 2017-10-27 CN CN201711038155.4A patent/CN107827938B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101012252A (en) * | 2007-01-30 | 2007-08-08 | 王成举 | Method of synthesizing 1,2,3-tri-O-acetyl-5-deoxidation-D-ribose |
| JP2009256335A (en) * | 2008-03-26 | 2009-11-05 | Univ Of Tokyo | Preparation method of ribonucleic acid having alkyl protective group at position 2' |
| CN102432642A (en) * | 2011-10-17 | 2012-05-02 | 江西科技师范学院 | Synthesis method of 1,2,3-O-triacetyl-5-deoxy-D-ribofuranose |
| CN104650160A (en) * | 2015-01-13 | 2015-05-27 | 济南大学 | Novel synthesis method of capecitabine key intermediate 1,2,3-O-triacetyl-5-deoxy-D-ribose |
Non-Patent Citations (3)
| Title |
|---|
| 1,2,3-O-三乙酰基-5-脱氧核糖的合成工艺研究;朱仁发 等;《安徽医药》;20080131;第12卷(第1期);第11-12页 * |
| Scalable Synthesis of a Nucleoside Phosphoramidate Prodrug Inhibitor of HCV NS5B RdRp: Challenges in the Production of a Diastereomeric Mixture;Benjamin A. Mayes等;《Org. Process Res. Dev.》;20150327;第19卷;第520-530页 * |
| 卡培他滨合成路线图解;何学军 等;《中国医药工业杂志》;20091231;第40卷(第7期);第549-551页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107827938A (en) | 2018-03-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114133350A (en) | Preparation method of anti-neocorolla drug Paxlovid intermediate | |
| CN1302004C (en) | Preparing method for cytarabine | |
| CN107827938B (en) | Preparation method of 1,2, 3-tri-O-acetyl-5-deoxy- β -D-ribose | |
| KR20110011917A (en) | Process for preparing of n-methyl pyrrolidone | |
| CN104045669A (en) | Separation method suitable for chemical synthesis of salidroside for industrial production | |
| CN111848679A (en) | Method for synthesizing Reidesvir by using microchannel reaction technology | |
| CN111393331B (en) | Preparation method of glycocyamine | |
| CN104961787B (en) | Synthetic method of cordycepin | |
| CN103665084A (en) | Method for preparing abiraterone acetate | |
| CN114213430B (en) | Preparation method of 4-aminothiophene [3,2-d ] pyrimidine-7-carboxylic acid and protein kinase inhibitor intermediate | |
| CN107216335B (en) | A kind of tert-butyl 1- (methylol) -3- oxa- -9- azaspiro [5.5] hendecane -9- formic acid base ester preparation method | |
| CN109836404B (en) | Epirubicin hydrochloride intermediate compound | |
| CN112958154B (en) | Application of silicon amino rare earth compound in catalyzing reaction of isatin compound and cyclopropenone compound | |
| CN114717280A (en) | Synthesis method of monopilavir | |
| CN103073525A (en) | Method for synthesizing (S)-(3,4-difluorophenyl)hexamethylene oxide | |
| CN109678738B (en) | Method for synthesizing (2S,3S) -3-amino-bicyclo [2.2.2] octane-2-formate | |
| CN113816837A (en) | Synthesis method of 4,4' -dimethoxy triphenylchloromethane | |
| CN104496900A (en) | Method for preparing 2-methoxy-6-one-5,7,8-trihydro-quinoline | |
| CN112939901A (en) | Preparation method of alpha-hydroxy-gamma-butyrolactone | |
| CN109942590B (en) | Preparation method of nitidine chloride | |
| CN111217709A (en) | Preparation method of (1-fluorocyclopropyl) methylamine hydrochloride | |
| CN106317064B (en) | The preparation method of methylnaltrexone bromide | |
| CN112409420B (en) | Purification method of 2 '-fluoro-2' -deoxyuridine | |
| CN113292610B (en) | Preparation method of natural product eutigoside C | |
| CN114773405B (en) | Preparation method of monatiravir |
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 | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Yang Xining Inventor after: Jin Haiyan Inventor after: Li Tao Inventor after: Cai Yuying Inventor after: Wang Xiuqiang Inventor before: Yang Xining Inventor before: Jin Haiyan Inventor before: Li Tao Inventor before: Cai Yuying Inventor before: Wang Xiuqiang |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |