CN107298680A - A kind of production technology of the azaindole of 4 chlorine 7 - Google Patents
A kind of production technology of the azaindole of 4 chlorine 7 Download PDFInfo
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- CN107298680A CN107298680A CN201710569208.9A CN201710569208A CN107298680A CN 107298680 A CN107298680 A CN 107298680A CN 201710569208 A CN201710569208 A CN 201710569208A CN 107298680 A CN107298680 A CN 107298680A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
A kind of production technology of the azaindole of 4 chlorine 7, comprises the following steps and the azaindole of N oxos 7 and tetrahydrofuran is added in reaction bulb, opens stirring；Mesyl chloride, natural heat release are added while stirring；Then simultaneously insulated and stirred to consumption of raw materials is finished for heating.Consumption of raw materials cools to 15 DEG C after finishing, control temperature is gone aqueous phase, be washed with water in 15 DEG C of 20 DEG C of dropwise addition sodium hydrate aqueous solutions, point liquid point；Organic phase rotates precipitation, obtains dark brown solid.Faint yellow solid is obtained with dichloromethane mashing, the azaindole of 4 chlorine 7 is obtained.With mesyl chloride simultaneously as chlorination reagent and dehydration reagent, cost is saved, operation difficulty is reduced.Using the special dissolution properties of product, it is beaten and is purified using the fabulous dichloromethane of solvability, effect is very good.It is easy to control, it is easy to industrialization, product purity is high.
Description
Technical field
The invention belongs to organic synthesis field, and in particular to a kind of preparation method of the chloro- 7- azaindoles of 4-.
Background technology
Azaindole is heterocyclic compound.There are a variety of isomers.7- azaindoles are the more commonly used medical industry synthesis
Intermediate, only can do a small amount of preparation using POCl3 at present, and yield is unstable, it is difficult to amplification production.4 substitution 7- nitrogen
Miscellaneous indoles, can be used as intermediate, the medicine for synthesizing with active anticancer or treating disease of immune system, with important
Medical value.But not a kind of stable amplification at present, reaction cost is low, it is easy to the production technology of purification.
Inventive method
In order to solve the above technical problems, the present invention provides a kind of production technology of the chloro- 7- azaindoles of 4-, including following step
Suddenly：
1. 250-400g, 1.87-2.97mol, 1.0eq. N- oxo -7- azaindoles and 2.1-3L tetra- are added in 5L reaction bulbs
Hydrogen furans, opens stirring；369-590g, 3.23-5.16mol, 1.73eq. mesyl chloride, natural heat release are added while stirring
To 50-55 DEG C；Consumption of raw materials after 55-60 DEG C of insulated and stirred 1-2h is then heated to finish.
2. 10-15 DEG C is cooled to after consumption of raw materials is finished, control temperature is in 15 DEG C of -20 DEG C of dropwise addition 750ml-1200ml hydrogen-oxygens
Change sodium water solution, point liquid point goes aqueous phase, uses 850ml-1.2L water washings；Organic phase rotates precipitation, obtains 170-260g dark-browns
Solid.
3. faint yellow solid 145-220g, yield 48.3%-51.0% are obtained with the mashing of 850ml-1.2L dichloromethane.
As a modification of the present invention, sulfonic acid chloride is used as chlorination reagent and dehydration reagent simultaneously.
The beneficial effects of the invention are as follows, simultaneously as chlorination reagent and dehydration reagent, saved cost with mesyl chloride, dropped
Low operation difficulty.Using the special dissolution properties of product, it is beaten and is purified using the fabulous dichloromethane of solvability, effect is non-
Chang Hao.It is easy to control, it is easy to industrialization, product purity is high.
Embodiment
In order to be better understood from the present invention, below by embodiment, the invention will be further described, and embodiment is only used for
The present invention is explained, any restriction is not constituted to the present invention.
A kind of embodiment 1, production technology of the chloro- 7- azaindoles of 4-, this method comprises the following steps:
1. 300g, 2.24mol are added in 5L reaction bulbs, 1.0eq. N- oxo -7- azaindoles and 2.5L tetrahydrofurans are opened
Stirring.The eq. mesyl chlorides of 443g, 3.87 mol, 1.73 are added while stirring, are added within 0.5 hour.Mesyl chloride conduct simultaneously
Chlorination reagent and dehydration reagent, it is cost-effective, operation difficulty is reduced, natural heat release is to 52 DEG C.55 DEG C of insulations are then heated to stir
Consumption of raw materials after 1h is mixed to finish.
2. 12 DEG C are cooled to after consumption of raw materials is finished, 900ml sodium hydrate aqueous solutions are added dropwise at 18 DEG C in control temperature, point liquid
Divide and go aqueous phase, use 1L water washings.Organic phase rotates precipitation, obtains 200g dark brown solids.
3. faint yellow solid 170g is obtained with the mashing of 1L dichloromethane.Dichloromethane solvability is fabulous, and mashing is extracted
The product purity come is high.Yield 49.8%.
A kind of embodiment 2, production technology of the chloro- 7- azaindoles of 4-, this method comprises the following steps:
1. 400g, 2.97mol are added in 5L reaction bulbs, 1.0eq. N- oxo -7- azaindoles and 3L tetrahydrofurans are opened
Stirring adds 590g while stirring, and 5.16mol, 1.73eq. mesyl chlorides are added for 0.5 hour.Mesyl chloride is used as chlorine simultaneously
Change reagent and dehydration reagent, it is cost-effective, operation difficulty is reduced, natural exotherm is then heated to 60 DEG C of insulations to 55 DEG C
Consumption of raw materials is finished after stirring 1h.
2. 15 DEG C are cooled to after consumption of raw materials is finished, 1200ml sodium hydrate aqueous solutions are added dropwise at 20 DEG C in control temperature, point
Liquid point goes aqueous phase, uses 1.2L water washings.Organic phase rotates precipitation, obtains 260g dark brown solids.
3. faint yellow solid 220g is obtained with the mashing of 1.2L dichloromethane.Dichloromethane solvability is fabulous, and mashing is refined
Product purity out is high.Yield 48.3%.
A kind of embodiment 3, production technology of the chloro- 7- azaindoles of 4-, this method comprises the following steps:
1. 250g, 1.87mol are added in 5L reaction bulbs, 1.0eq. N- oxo -7- azaindoles and 2.1L tetrahydrofurans are opened
Stirring.369g is added while stirring, and 3.23mol, 1.73eq. mesyl chlorides are added for 0.5 hour.Mesyl chloride is used as chlorine simultaneously
Change reagent and dehydration reagent, it is cost-effective, operation difficulty is reduced, natural exotherm is then heated to 55 DEG C of insulations to 50 DEG C
Consumption of raw materials is finished after stirring 1h.
2. 10 DEG C are cooled to after consumption of raw materials is finished, 750ml sodium hydrate aqueous solutions are added dropwise at 15 DEG C in control temperature, point liquid
Divide and go aqueous phase, use 850ml water washings.Organic phase rotates precipitation, obtains 170 dark brown solids.
3. faint yellow solid 145g is obtained with the mashing of 850ml dichloromethane.Dichloromethane solvability is fabulous, and mashing is refined
Product purity out is high.Yield 51.0%.
Claims (2)
1. a kind of production technology of the chloro- 7- azaindoles of 4-, comprises the following steps：
1. 250-400g, 1.87-2.97mol, 1.0 eq. N- oxo -7- azaindoles and 2.1-3L are added in 5L reaction bulbs
Tetrahydrofuran, opens stirring；369-590g is added while stirring, and 3.23-5.16 mol, 1.73eq. mesyl chloride are put naturally
Heat is to 50-55 DEG C；Consumption of raw materials after 55-60 DEG C of insulated and stirred 1-2h is then heated to finish；
2. 10-15 DEG C is cooled to after consumption of raw materials is finished, control temperature is in 15 DEG C of -20 DEG C of dropwise addition 750ml-1200ml sodium hydroxides
The aqueous solution, point liquid point goes aqueous phase, uses 850ml-1.2L water washings；Organic phase rotates precipitation, obtains 170-260g dark brown solids；
3. faint yellow solid 145-220g, yield 48.3%-51.0% are obtained with the mashing of 850ml-1.2L dichloromethane.
2. according to a kind of production technology of the chloro- 7- azaindoles of 4- described in claim 1, it is characterised in that the sulfonic acid chloride
It is used as chlorination reagent and dehydration reagent simultaneously.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710569208.9A CN107298680A (en) | 2017-07-12 | 2017-07-12 | A kind of production technology of the azaindole of 4 chlorine 7 |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710569208.9A CN107298680A (en) | 2017-07-12 | 2017-07-12 | A kind of production technology of the azaindole of 4 chlorine 7 |
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| CN201710569208.9A Pending CN107298680A (en) | 2017-07-12 | 2017-07-12 | A kind of production technology of the azaindole of 4 chlorine 7 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090181959A1 (en) * | 2005-12-13 | 2009-07-16 | Incyte Corporation | HETEROARYL SUBSTITUTED PYRROLO[2,3-b]PYRIDINES AND PYRROLO[2,3-b]PYRIMIDINES AS JANUS KINASE INHIBITORS |
| CN102741266A (en) * | 2009-10-06 | 2012-10-17 | 塔古西库斯生物株式会社 | Artificial base pair capable of forming specific base pair |
| EP2955181A1 (en) * | 2013-02-08 | 2015-12-16 | Nissan Chemical Industries, Ltd. | Tricyclic pyrrolopyridine compound, and jak inhibitor |
-
2017
- 2017-07-12 CN CN201710569208.9A patent/CN107298680A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090181959A1 (en) * | 2005-12-13 | 2009-07-16 | Incyte Corporation | HETEROARYL SUBSTITUTED PYRROLO[2,3-b]PYRIDINES AND PYRROLO[2,3-b]PYRIMIDINES AS JANUS KINASE INHIBITORS |
| CN102741266A (en) * | 2009-10-06 | 2012-10-17 | 塔古西库斯生物株式会社 | Artificial base pair capable of forming specific base pair |
| EP2955181A1 (en) * | 2013-02-08 | 2015-12-16 | Nissan Chemical Industries, Ltd. | Tricyclic pyrrolopyridine compound, and jak inhibitor |
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Application publication date: 20171027 |