CN104829616A - Synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone - Google Patents
Synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone Download PDFInfo
- Publication number
- CN104829616A CN104829616A CN201510199809.6A CN201510199809A CN104829616A CN 104829616 A CN104829616 A CN 104829616A CN 201510199809 A CN201510199809 A CN 201510199809A CN 104829616 A CN104829616 A CN 104829616A
- Authority
- CN
- China
- Prior art keywords
- pyridine
- phenyl ketone
- chlorine imidazo
- synthetic method
- hours
- 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
Classifications
-
- 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
Abstract
The invention relates to a synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone. The method includes: reacting N, N-dimethylformamide dimethylacetal with 2-amino-5-chloropyridine at 40-100DEG C to obtain an N, N-dimethyl-N'-2-(5-chloro-pyridine)yl-carboxamidine intermediate; without purification and under the action of alkali, subjecting the intermediate and alpha-chloroacetophenone to reaction at 60-160DEG C in certain solvent, at the end of the reaction, performing cooling to room temperature, precipitating high purity 6-chloroimidazo[1, 2-a]pyridine3-phenyl ketone crystals, conducting pumping filtration, collecting the filter cake, adding water to the mother solution, carrying out extraction, washing, drying and concentrating to obtain a crude product, recrystallizing the crude product to obtain a pure product. The reaction raw materials are easily available, the prices are reasonable, the reaction conditions are mild, the method is easy to operate and control, the aftertreatment is simple, and the product has stable quality and high purity.
Description
(1) technical field
The invention belongs to organic synthesis field, be specifically related to a kind of synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone.
(2) background technology
Phenyl ketone derivative is as 3, 5-difluorophenyl ketone, generally by 3, 5-difluorobenzonitrile and alkyl Grignard reagent reaction preparation corresponding 3, 5-difluorophenyl ketone, as 3, preparation 3 is hydrolyzed after 5-difluorobenzonitrile and Grignard reagent ethyl phosphonium bromide reactive magnesium, 5-difluorobenzene acetone, this method reaction conditions is gentle, operate easier, but raw material 3, 5-difluorobenzonitrile is expensive, and reaction solvent for use is lower boiling ether, be that solvent scale operation danger is larger with it, the waste residue simultaneously produced in last handling process and waste liquid amount larger, its large-scale production is restricted.
Or with 2,4-difluoroaniline for starting raw material, through diazotization reaction salify, then with ethylidenehydroxylamine coupling, hydrolyzed under acidic conditions prepares 2,4-difluoro acetophenone.This method reaction conditions is gentleer, and cost of material is comparatively cheap, and yield is higher, but operates tediously long complexity, has used the raw material of this instability of ethylidenehydroxylamine in reaction, and temperature of reaction control ratio is harsher, comparatively large on yield impact, is unfavorable for large-scale production.
A kind of method preparing fluorine-containing substituted phenyl ketone that on June 20th, 2012 announces, concrete preparation process is as follows:
(1) in reactor, ether solvent is added, magnesium powder, drip the ether solvent containing main raw material fluoro bromobenzene, prepare grignard reagent flourophenyl magnesium bromide, wherein, the mol ratio of main raw material fluoro bromobenzene and magnesium powder is 1.0: 1.2 ~ 1.8, and main raw material fluoro bromobenzene is 1g/3 ~ 8mL with the amount ratio of the ether solvent that first time adds, and main raw material fluoro bromobenzene is 1g/1 ~ 4mL with the amount ratio of the ether solvent that second time adds;
(2) in another reactor, ether solvent is added successively, metal catalyst, Lewis acid aluminum chloride, acid anhydrides, temperature control 5 ~ 15 DEG C drips grignard reagent flourophenyl magnesium bromide prepared by step (1), dripping finishes in this thermotonus 3 ~ 6h, wherein, the mol ratio of main raw material fluoro bromobenzene and metal catalyst is 1.0: 0.05 ~ 0.1, the mol ratio of main raw material fluoro bromobenzene and aluminum chloride is 1.0: 0.05 ~ 0.1, the mol ratio of main raw material fluoro bromobenzene and acid anhydrides is 1.0: 1.5 ~ 2.5, the amount ratio of main raw material fluoro bromobenzene and ether solvent is 1g/2 ~ 7mL,
(3) reaction is finished, extraction, the water washing of organic phase salt, and concentrated product fluorine-containing substituted phenyl ketone wherein R is-CH
2c
nh
(2n+1)(n=0,1,2,3,4,5), fluorine be ortho position, a position, contraposition, 2 and 4,2 and 3,3 and 5.
Aforesaid method cheaper starting materials is easy to get, and reaction purity and yield is all higher, and stable process conditions is simple to operate, is applicable to large-scale production.
6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone is the important intermediate of organic synthesis, is mainly used in medicine intermediate, organic synthesis, organic solvent, also can be applicable to the aspects such as DYE PRODUCTION, pesticide producing and spices.This heterogeneous ring compound is new synthesis, and product is novel, has very large value.
(3) summary of the invention
The present invention needs the problem solved to be for prior art, the invention provides a kind of synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone, and this brand-new compound has very large Application in Chemical Engineering and is worth.Technique is simple, and meet the chemical concept of environmental protection, this synthetic method is simple to operate, productive rate is high, is applicable to laboratory and suitability for industrialized production.
The present invention is achieved through the following technical solutions:
A kind of synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone, its special character is: comprise the following steps:
(1) N is prepared, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate: N, dinethylformamide dimethylacetal and 2-amino-5-chloropyridine react obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate at 40-100 DEG C;
(2) 6-chlorine imidazo [1 is prepared, 2-a] pyridine-3-phenyl ketone: above-mentioned intermediate does not need to purify, under alkali effect, in certain solvent, react at 60-160 DEG C with alpha-chloro acetophenone, reaction terminates, be chilled to room temperature, there is highly purified 6-chlorine imidazo [1, 2-a] precipitation of pyridine 3-phenyl ketone crystal, suction filtration, collect filter cake, mother liquor adds water, extraction into ethyl acetate, water and saturated common salt water washing, anhydrous sodium sulfate drying, 6-chlorine imidazo [1 is obtained after rotary evaporation is concentrated, 2-a] the thick product of pyridine 3-phenyl ketone, this thick product recrystallization obtains sterling.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, temperature described in step (1) is 40 DEG C, 60 DEG C, 80 DEG C, 100 DEG C.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, reaction times 2-8 hour described in step (2).
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, the reaction times described in step (1) is 3 hours, 6 hours, 8 hours.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, described in step (2), solvent is dioxane, toluene, DMF, at least one in N,N-dimethylacetamide.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, described in step (2), alkali is saleratus, salt of wormwood, sodium bicarbonate, sodium carbonate, sodium hydroxide, at least one in potassium hydroxide.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, temperature described in step (2) is 60 DEG C, 100 DEG C, 120 DEG C, 160 DEG C.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, the reaction times described in step (2) is 3-15 hour.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, the reaction times described in step (2) is 8 hours, 10 hours, 12 hours, 15 hours.
The synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone of the present invention, with the normal hexane of volume ratio 3:1 and ethyl acetate mixture recrystallization in step (2).
Its reaction is:
Beneficial effect of the present invention: reaction raw materials compares and is easy to get, reasonable price, reaction conditions is gentle, easy handling, is easy to control, and aftertreatment is simple, and constant product quality, purity is high.
(4) embodiment
Embodiment 1
80mL (71.7g, 600mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, reacts 3 hours with at 2-amino-5-chloropyridine (25.6g, 200mmol) 40 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary DMF dimethylacetal, add 120 ml(125g) dioxane, NaHCO
3(25.2g, 300mmol) and alpha-brominated methyl phenyl ketone (59.7g, 300mmol), 100 DEG C are reacted 10 hours, reaction terminates, and is chilled to room temperature, is placed on refrigeration chamber 3 hours, suction filtration, obtains 26.5g high purity 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 17.4g, altogether obtain 48.4g product, productive rate 84.7%, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.95 (d, J=9.6Hz, 1H) 7.884 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.691 (t, J=7.6Hz, 1H), 7.596 (t, J=7.6Hz, 2H).
Embodiment 2
80mL (71.7g, 600mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, reacts 6 hours with at 2-amino-5-chloropyridine (25.6g, 200mmol) 80 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary DMF dimethylacetal, add 120 ml(125g) dioxane, NaHCO
3(25.2g, 300mmol) and alpha-brominated methyl phenyl ketone (47.76g, 240mmol), 120 DEG C are reacted 8 hours, reaction terminates, and is chilled to room temperature, is placed on refrigeration chamber 3 hours, suction filtration, obtains 29g highly purified 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 20.5g, altogether obtain 49.5g product, productive rate 82.2%, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.95 (d, J=9.6Hz, 1H) 7.884 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.691 (t, J=7.6Hz, 1H), 7.596 (t, J=7.6Hz, 2H).
Embodiment 3
80mL (71.7g, 600mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 3 hours at 100 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 120 ml(125g) DMF, sodium hydroxide (12g, 300mmol) with alpha-brominated methyl phenyl ketone (59.7g, 300mmol), 160 DEG C are reacted 8 hours, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 28g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 19.3g, altogether obtain 47.3g product, productive rate 78.57%, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.95 (d, J=9.6Hz, 1H) 7.884 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.691 (t, J=7.6Hz, 1H), 7.596 (t, J=7.6Hz, 2H).
Embodiment 4
67ml(60.08g, 500mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 8 hours at 100 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 120 ml(125g) dioxane, potassium hydroxide (16.8g, 300mmol) with alpha-brominated methyl phenyl ketone (59.7g, 300mmol), 100 DEG C are reacted 12 hours, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 28.8g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 21.3g, altogether obtain 50.1g product, productive rate 83.22%, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.95 (d, J=9.6Hz, 1H) 7.884 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.691 (t, J=7.6Hz, 1H), 7.596 (t, J=7.6Hz, 2H).
Embodiment 5
80mL (71.7g, 600mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 7 hours at 60 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 120 ml toluene, salt of wormwood (300mmol) and alpha-brominated methyl phenyl ketone (59.7g, 300mmol), 60 DEG C are reacted 15 hours, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 28g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 19.2g, altogether obtain 47.2g product, productive rate 78.56%, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.94 (d, J=9.6Hz, 1H) 7.883 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.690 (t, J=7.6Hz, 1H), 7.594 (t, J=7.6Hz, 2H).
Embodiment 6
80mL (71.7g, 600mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 7 hours at 80 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 120 mlN, N-N,N-DIMETHYLACETAMIDE, saleratus (300mmol) and alpha-brominated methyl phenyl ketone (59.7g, 300mmol), 93 DEG C are reacted 11 hours, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 28g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 19.2g, altogether obtain 47.2g product, productive rate 78.56%, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.94 (d, J=9.6Hz, 1H) 7.883 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.689 (t, J=7.6Hz, 1H), 7.592 (t, J=7.5Hz, 2H).
Embodiment 7
80mL (71.7g, 600mmol) N, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 7 hours at 80 DEG C, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 120 mlN, N-N,N-DIMETHYLACETAMIDE, sodium carbonate (300mmol) and alpha-brominated methyl phenyl ketone (280mmol), 101 DEG C are reacted 10 hours, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 28g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4dry, filter, 6-chlorine imidazo [1 is obtained after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 19.2g, altogether obtain 47.2g product, fusing point: 137.8-138.2 DEG C, 1HNMR (400MHz, DMSO) δ: 9.684 (s, 1H), 8.309 (s, 1H), 7.94 (d, J=9.6Hz, 1H) 7.883 (d, J=7.2Hz, 2H), 7.79 (d, J=9.2Hz, 1H), 7.686 (t, J=7.5Hz, 1H), 7.591 (t, J=7.5Hz, 2H).
Embodiment 8
380mmolN, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 0.5 hour at 102 DEG C, then 7ml toluene is added, salt of wormwood (0.4g) and alpha-brominated methyl phenyl ketone (5g), react 0.5 hour, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 220 ml toluene, salt of wormwood (300mmol) and alpha-brominated methyl phenyl ketone (55g), 110 DEG C are reacted 1 hour, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 28.7g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4drying, filters, and obtains 6-chlorine imidazo [1 after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 20.1g, altogether 48.8g product, fusing point: 137.8-138.2 DEG C.
Embodiment 9
380mmolN, dinethylformamide dimethylacetal is solvent and reaction raw materials, with 2-amino-5-chloropyridine (25.6g, 200mmol) reaction 0.5 hour at 102 DEG C, then 7mlN is added, N-N,N-DIMETHYLACETAMIDE, salt of wormwood (0.4g) and alpha-brominated methyl phenyl ketone (5g), 103 DEG C are reacted 0.5 hour, reaction terminates obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate, rotary evaporation removes unnecessary N, dinethylformamide dimethylacetal, add 220 mlN, N-N,N-DIMETHYLACETAMIDE, salt of wormwood (300mmol) and alpha-brominated methyl phenyl ketone (54g), 166 DEG C are reacted 1 hour, reaction terminates, be chilled to room temperature, be placed on refrigeration chamber 3 hours, suction filtration, obtain 30g high purity 6-chlorine imidazo [1, 2-a] pyridine-3-phenyl ketone crystal.Mother liquor adds 600 ml water and 200 ml extraction into ethyl acetate, separates organic phase, and aqueous phase is extracted with ethyl acetate (3 × 200 ml), merges organic phase, washes with water (2 × 150 ml), 200 ml saturated common salt water washings, anhydrous Na
2sO
4drying, filters, and obtains 6-chlorine imidazo [1 after filtrate is concentrated, 2-a] the thick product of pyridine-3-phenyl ketone, this thick product is through normal hexane: ethyl acetate=3:1(volume ratio) mixing solutions recrystallization obtain sterling 20.0g, altogether 50.0g product, fusing point: 137.8-138.1 DEG C.
Claims (10)
1. the synthetic method of 6-chlorine imidazo [1, a 2-a] pyridine-3-phenyl ketone, is characterized in that: comprise the following steps:
(1) N is prepared, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate: N, dinethylformamide dimethylacetal and 2-amino-5-chloropyridine react obtained N, N-dimethyl-N'-2-(the chloro-pyridine of 5-) base-carbonamidine intermediate at 40-100 DEG C;
(2) 6-chlorine imidazo [1 is prepared, 2-a] pyridine-3-phenyl ketone: above-mentioned intermediate does not need to purify, under alkali effect, in certain solvent, react at 60-160 DEG C with alpha-chloro acetophenone, reaction terminates, be chilled to room temperature, there is highly purified 6-chlorine imidazo [1, 2-a] precipitation of pyridine 3-phenyl ketone crystal, suction filtration, collect filter cake, mother liquor adds water, extraction into ethyl acetate, water and saturated common salt water washing, anhydrous sodium sulfate drying, 6-chlorine imidazo [1 is obtained after rotary evaporation is concentrated, 2-a] the thick product of pyridine 3-phenyl ketone, this thick product recrystallization obtains sterling.
2. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1, is characterized in that: temperature described in step (1) is 40 DEG C, 60 DEG C, 80 DEG C, 100 DEG C.
3. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1 and 2, is characterized in that: reaction times 2-8 hour described in step (2).
4. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 3, is characterized in that: the reaction times described in step (1) is 3 hours, 6 hours, 8 hours.
5. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1 and 2, is characterized in that: described in step (2), solvent is dioxane, toluene, DMF, at least one in N,N-dimethylacetamide.
6. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1 and 2, is characterized in that: described in step (2), alkali is saleratus, salt of wormwood, sodium bicarbonate, sodium carbonate, sodium hydroxide, at least one in potassium hydroxide.
7. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1 and 2, is characterized in that: temperature described in step (2) is 60 DEG C, 100 DEG C, 120 DEG C, 160 DEG C.
8. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1 and 2, is characterized in that: the reaction times described in step (2) is 3-15 hour.
9. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 8, is characterized in that: the reaction times described in step (2) is 8 hours, 10 hours, 12 hours, 15 hours.
10. the synthetic method of 6-chlorine imidazo [1,2-a] pyridine-3-phenyl ketone according to claim 1 and 2, is characterized in that: with the normal hexane of volume ratio 3:1 and ethyl acetate mixture recrystallization in step (2).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510199809.6A CN104829616A (en) | 2015-04-25 | 2015-04-25 | Synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510199809.6A CN104829616A (en) | 2015-04-25 | 2015-04-25 | Synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104829616A true CN104829616A (en) | 2015-08-12 |
Family
ID=53807855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510199809.6A Pending CN104829616A (en) | 2015-04-25 | 2015-04-25 | Synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104829616A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965192A (en) * | 2014-05-20 | 2014-08-06 | 定陶县友帮化工有限公司 | Synthesis method of 6-chloroimidazo[1,2-alpha]pyridyl-3-formic acid |
-
2015
- 2015-04-25 CN CN201510199809.6A patent/CN104829616A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965192A (en) * | 2014-05-20 | 2014-08-06 | 定陶县友帮化工有限公司 | Synthesis method of 6-chloroimidazo[1,2-alpha]pyridyl-3-formic acid |
Non-Patent Citations (1)
| Title |
|---|
| HUA CAO ETAL: "Transition Metal-Mediated C=O and C=C Bond-Forming Reactions:A Regioselective Strategy for the Synthesis of Imidazo[1,2-a]pyridines and Imidazo[1,2-a]pyrazines", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100888124B1 (en) | Method for producing polyhalogenated diamantane and derivative thereof | |
| CN106279074A (en) | A kind of compound and preparation method thereof and the purposes in synthesis Bu Waxitan | |
| CN103497226B (en) | Refinement method of methylamino abamectin benzoate | |
| CN106748921B (en) | A kind of virtue sulfuryl difluoroacetic acid salt compounds, preparation method and applications | |
| CN106365986A (en) | Compounds and preparation methods thereof, and uses of compounds in synthesis of brivaracetam | |
| CN104610066B (en) | The preparation method of fluoro-4, the 6-dinitroresorcinols of a kind of 2,5-bis- | |
| CN109232212B (en) | Method for synthesizing methyl heptenone from isopentenol | |
| CN105037138A (en) | Preparation method for 2,9-dibutyl sebacate | |
| CN103965191A (en) | Synthesis method of 6-bromoimidazo[1,2-alpha]pyridyl-3-formic acid | |
| CN103396318A (en) | Synthetic process for 2,4-dinitroanisole | |
| CN104829615A (en) | Synthesis method for 6-fluoroimidazo[1, 2-a]pyridine-3-phenyl ketone | |
| CN104829616A (en) | Synthesis method for 6-chloroimidazo[1, 2-a]pyridine-3-phenyl ketone | |
| CN104844596A (en) | Synthesis method for 6-bromoimidazo[1, 2-a]pyridine-3-phenyl ketone | |
| CN106117060A (en) | A kind of purification process of 7 chlorine 2 oxoheptanoates | |
| CN108864173B (en) | Process for converting substituted sodium arylsulfinates into aryltri-n-butyltin | |
| CN103087090A (en) | Synthetic method of 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine | |
| CN106749156B (en) | Process for preparing benzo [1,3-d ] dioxoles and intermediates thereof | |
| CN110759840A (en) | Synthesis method of 1, 1-dibromo-2, 2-bis (chloromethyl) cyclopropane | |
| CN104844595A (en) | Synthesis method for imidazo[1, 2-a]pyridine-3-phenyl ketone | |
| CN111574384A (en) | Preparation method of chiral 1-amino-2-propanol | |
| CN110128347A (en) | A kind of synthetic method of 1- methyl-1 H- indazole -6- formic acid | |
| CN103864786A (en) | Method for synthesizing 6-fluoroimidazo-[1,2-a]-pyridine-3-formic acid | |
| CN104177290A (en) | New synthesis technique of 3,5,6-trichloropyridyl-2-sodium alkoxide | |
| CN109879815B (en) | 2-bromo-6-aldehyde pyridine and preparation method thereof | |
| CN103965192A (en) | Synthesis method of 6-chloroimidazo[1,2-alpha]pyridyl-3-formic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150812 |