CN105968106B - The synthetic method of 2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3- base) acetamide - Google Patents
The synthetic method of 2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3- base) acetamide Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
The invention belongs to pharmaceutical technology fields, relate generally to a kind of Cefotiam process impurity: the synthetic method of 2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3- base) acetamide.The method of the invention is using Cefotiam as raw material, dissolution is in a solvent, in the presence of hydrogen peroxide, it is reacted in alkaline solution, it adjusts pH to faintly acid, filters, washing, 2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3- base) acetamid impurity is obtained, reaction equation is as follows:
Description
Technical field
The invention belongs to pharmaceutical technology fields, relate generally to a kind of Cefotiam process impurity: 2- (thiazolamine -4-
Base)-N- (2- oxygroup azetidin -3- base) acetamide synthetic method.
Background technique
Cefotiam, also known as (6R- is trans-) -7- [[(2- amino -4- thiazolyl) acetyl group] amino] -3- [[[1- [(2-
(dimethylamino) ethyl] -1H-TETRAZOLE -5- base] sulphomethyl] -8- oxo -5- thia -1- azabicyclo [4.2.0] octyl- 2-
Alkene -2- carboxylic acid dihydrochloride.Its structural formula are as follows:
Cefotiam is developed by Japanese Takede Chemical Industries Ltd earliest, and product is dihydrochloride, and added with
A certain amount of natrium carbonicum calcinatum.Its dihydrochloride is commonly used, is powder white or yellowish；It is slightly special smelly；Add water i.e. effervesce molten
Solution generates the clear solution of weakly acidic pH, is slightly soluble in ethyl alcohol, insoluble in acetone chloroform.
Since impurity of the drug is studied in pharmaceutical process, optimization and quality control aspect are extremely important, thus Cefotiam work
The miscellaneous Quality Research of skill is also very necessary.
By consulting literatures discovery, there is presently no document reports to cross Cefotiam process impurity 2- (thiazolamine -4-
Base)-N- (2- oxygroup azetidin -3- base) acetamide preparation.
Summary of the invention
In view of this, present invention firstly discloses a kind of Cefotiam process impurity 2- (thiazolamine -4- base)-N-
The synthetic method of (2- oxygroup azetidin -3- base) acetamide.
The method of the invention is using Cefotiam as raw material, and dissolution is in a solvent, molten in alkalinity in the presence of hydrogen peroxide
It is reacted in liquid, adjusts pH to faintly acid, filter, washing obtains 2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3-
Base) acetamid impurity, reaction equation is as follows:
Present invention firstly discloses a kind of Cefotiam process impurity 2- (thiazolamine -4- base)-N- (2- oxygroup azepines
Ring butyl- 3- yl) acetamide synthetic method.Using Cefotiam as raw material, dissolution in a solvent, exists the present invention in hydrogen peroxide
Under, it is reacted in alkaline solution, adjusts pH to faintly acid, filter, washing obtains 2- (thiazolamine -4- base)-N- (2- oxygroup
Azetidin -3- base) acetamid impurity.
Preferably, hydrogen peroxide is added during the reaction.
Preferably, alkali used in the reaction is 32% concentrated ammonia liquor, triethylamine, sodium carbonate, potassium carbonate, sodium bicarbonate, bicarbonate
Potassium, sodium hydroxide, any one in potassium hydroxide.It is preferred that 32% concentrated ammonia liquor.
Preferably, which is methanol, ethyl alcohol, acetone, any one in water.It is preferred that water.
Preferably, spore is 1:110 for the molar equivalent ratio of peace and water.
Preferably, the molar equivalent of Cefotiam and hydrogen peroxide ratio is 1:17.
Preferably, the molar equivalent of Cefotiam and 32% concentrated ammonia liquor ratio is 1:13.
Preferably, Cefotiam: solvent: hydrogen peroxide: the molar equivalent ratio of alkali is 1:100~200:10~20:10~20.
It is preferred that 1:110:17:13.
Preferably, this method range of reaction temperature is 0~60 DEG C.It is preferred that 25 DEG C.
Preferably, this method reaction time is 3~12h.It is preferred that 6h.
By using above-mentioned technology, the present invention has good reaction selectivity, and synthetic operation is easy, and reaction condition is mild, easily
In purification process, high income, purity is high can be used as the necessity of Cefotiam quality control or be applied to Cefotiam impurity pair
The features such as according to product research.
Specific embodiment
The invention will be further described by way of example again below, provides implementation detail of the invention, but be not
It is intended to limit the scope of protection of the present invention.
Embodiment 1
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 19.4g, yield 86%, liquid phase
Purity 99.8%.1H-NMR(DMSO-d6): 8.40 (s, 1H), 7.11 (t, J=11Hz, 1H), 6.85 (s, 2H), 6.29 (s,
1H), 5.72 (d, J=10Hz, 2H), 3.35 (s, 2H)13C-NMR(DMSO-d6):171.6,169.1,169.0,150.8,
104.3,55.4,40.1,33.1.LC-MS[M+H]+:227.1.
HPLC testing conditions are as follows:
Pillar: CAPCELL PAK ACR-C18 liquid-phase chromatographic column, internal diameter 4.6mm, length 25cm, 5 μm of particle diameter.Column
Temperature: 35 DEG C.Detection wavelength: 254nm.Flow velocity: 1ml/min.Mobile phase: phosphate buffer (uses the phosphoric acid hydrogen of 0.05mol/L
The potassium dihydrogen phosphate of disodium and 0.05mol/L are prepared, and pH is adjusted to 7.6-7.8 (volume ratio about 4:1)) it is used as eluent A,
Acetonitrile is as eluent B.
Embodiment 2
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), triethylamine 180ml (1.3mol), 25 DEG C of reaction 6h are precipitated pale yellow with 1N concentrated hydrochloric acid tune pH to 5.8
Color solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 2.9g, yield 13%, liquid phase purity
95.5%.
Embodiment 3
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Yellow is precipitated with 1N concentrated hydrochloric acid tune pH to 5.8 in oxygen water 50ml (1.7mol), sodium carbonate 137.8g (1.3mol), 25 DEG C of reaction 6h
Solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains yellow target product 1.1g, yield 5%, liquid phase purity
94.1%.
Embodiment 4
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), sodium hydroxide 52g (1.3mol), 25 DEG C of reaction 6h can only be passed through with 1N concentrated hydrochloric acid tune pH to 5.8
Efficient liquid phase monitoring discovery reaction solution contains a small amount of target product.
By comparing embodiment 1 and embodiment 2, embodiment 3, embodiment 4 and triethylamine, sodium carbonate, sodium hydroxide phase
Than the reaction yield highest of 32% concentrated ammonia liquor.
Embodiment 5
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, methanol 446ml (11mol) is sequentially added,
Hydrogen peroxide 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains yellow target product 1.6g, yield 7%, liquid phase purity
92.8%.
Embodiment 6
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, acetone 818ml (11mol) is sequentially added,
Hydrogen peroxide 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains yellow target product 0.5g, yield 2%, liquid phase purity
88.1%.
It is compared by comparing embodiment 1 and embodiment 5, embodiment 6 with methanol, acetone, reaction yield of the water as solvent
Highest.
Embodiment 7
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 182ml (10mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 18.8g, yield 83%, liquid phase
Purity 99.8%.
Embodiment 8
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 364ml (20mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 18.3g, yield 81%, liquid phase
Purity 99.8%.
By comparing embodiment 1 and embodiment 7, embodiment 8, the molar equivalent ratio of Cefotiam and water is anti-when being 1:110
Answer effect best.
Embodiment 9
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 29.4ml (1.0mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated with 1N concentrated hydrochloric acid tune pH to 5.8
Light yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 14.9g, yield 66%, liquid
Phase purity 99.5%.
Embodiment 10
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 59ml (2.0mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 19.0g, yield 84%, liquid phase
Purity 99.7%.
Embodiment 11
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, water 200ml (11mol) is sequentially added,
32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 6h can only be monitored by efficient liquid phase and be sent out with 1N concentrated hydrochloric acid tune pH to 5.8
Existing reaction solution contains a small amount of target product.
By comparing embodiment 1 and embodiment 9, embodiment 10, embodiment 11, it has been found that dioxygen water energy significantly improves instead
Answer yield, reaction effect is best when the molar equivalent ratio of Cefotiam and hydrogen peroxide is 1:17.
Embodiment 12
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 38ml (1.0mol), 25 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 18.1g, yield 80%, liquid phase
Purity 99.8%.
Embodiment 13
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 77ml (2.0mol), 25 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 18.3g, yield 81%, liquid phase
Purity 99.5%.
By comparing embodiment 1 and embodiment 12, embodiment 13, it has been found that mole of Cefotiam and 32% concentrated ammonia liquor
Reaction effect is best when equivalent proportion is 1:13.
To sum up, the preferred Cefotiam of the present invention: solvent: hydrogen peroxide: the molar equivalent ratio of alkali is 1:110:17:13.
Embodiment 14
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 0 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 12.7g, yield 56%, liquid phase
Purity 99.8%.
Embodiment 15
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 60 DEG C of reaction 6h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 7.2g, yield 32%, liquid-phase pure
Degree 99.1%.
By comparing embodiment 1 and embodiment 14, embodiment 15, it has been found that reaction temperature be 25 DEG C when reaction effect most
It is good.
Embodiment 16
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 3h are precipitated shallow with 1N concentrated hydrochloric acid tune pH to 5.8
Yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 18.0g, yield 80%, liquid phase
Purity 99.8%.
Embodiment 17
Cefotiam 52.5g (0.1mol) addition mono- neck of 500ml is lacked in bottle, is sequentially added water 200ml (11mol), it is double
Oxygen water 50ml (1.7mol), 32% concentrated ammonia liquor 50ml (1.3mol), 25 DEG C of reaction 12h are precipitated with 1N concentrated hydrochloric acid tune pH to 5.8
Light yellow solid, filtering, filter residue is successively washed with water to be washed with a small amount of acetone, obtains light yellow target product 18.5g, yield 82%, liquid
Phase purity 99.8%.
By comparing embodiment 1 and embodiment 16, embodiment 17, it has been found that the reaction time be 6h when reaction effect most
It is good.
After having read the explanation of this method, those skilled in the art can make various changes or modification to the present invention,
Such equivalent forms equally fall within the limited range of the application the appended claims.
Claims (6)
- The synthetic method of 1.2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3- base) acetamide, it is characterised in that: Using Cefotiam as raw material, dissolution in a solvent, in the presence of hydrogen peroxide, is reacted in alkaline solution, adjusts pH to faintly acid, mistake Filter, washing, obtains 2- (thiazolamine -4- base)-N- (2- oxygroup azetidin -3- base) acetamide；The alkaline solution is 32% concentrated ammonia liquor；The reaction solvent for use is water.
- 2. synthetic method according to claim 1, it is characterised in that: hydrogen peroxide is added during the reaction.
- 3. synthetic method according to claim 1, it is characterised in that: Cefotiam: solvent: hydrogen peroxide: alkali mole is worked as Amount is than being 1:100~200:10~20:10~20.
- 4. synthetic method according to claim 3, it is characterised in that: Cefotiam: solvent: hydrogen peroxide: alkali mole is worked as Amount is than being 1:110:17:13.
- 5. synthetic method according to claim 1, it is characterised in that: this method range of reaction temperature is 0~60 DEG C.
- 6. synthetic method according to claim 1, it is characterised in that: this method reaction time is 3~12h.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101619069A (en) * | 2009-07-28 | 2010-01-06 | 余小强 | Preparation method of cefotiam hexetil hydrochloride |
| CN101948476A (en) * | 2010-09-19 | 2011-01-19 | 苏州致君万庆药业有限公司 | Method for preparing cefotiam hexetil hydrochloride |
| CN102850381A (en) * | 2012-10-10 | 2013-01-02 | 山东金城医药化工股份有限公司 | Preparation method of cefotiam hydrochloride crude product |
| CN103570745A (en) * | 2013-10-10 | 2014-02-12 | 哈药集团制药总厂 | Preparation method of cefotiam hydrochloride lactone |
| CN105017173A (en) * | 2015-06-18 | 2015-11-04 | 广州白云山天心制药股份有限公司 | Cefotiam impurity A derivative preparation method |
-
2016
- 2016-05-12 CN CN201610312720.0A patent/CN105968106B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101619069A (en) * | 2009-07-28 | 2010-01-06 | 余小强 | Preparation method of cefotiam hexetil hydrochloride |
| CN101948476A (en) * | 2010-09-19 | 2011-01-19 | 苏州致君万庆药业有限公司 | Method for preparing cefotiam hexetil hydrochloride |
| CN102850381A (en) * | 2012-10-10 | 2013-01-02 | 山东金城医药化工股份有限公司 | Preparation method of cefotiam hydrochloride crude product |
| CN103570745A (en) * | 2013-10-10 | 2014-02-12 | 哈药集团制药总厂 | Preparation method of cefotiam hydrochloride lactone |
| CN105017173A (en) * | 2015-06-18 | 2015-11-04 | 广州白云山天心制药股份有限公司 | Cefotiam impurity A derivative preparation method |
Non-Patent Citations (1)
| Title |
|---|
| 注射用盐酸头孢替安有关物质测定方法研究;周冉，等;《中国抗生素杂志》;20140831;第39卷(第8期);第604-607页 |
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