CN104098517A - Lapatinib intermediate preparation method - Google Patents
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- CN104098517A CN104098517A CN201310121641.8A CN201310121641A CN104098517A CN 104098517 A CN104098517 A CN 104098517A CN 201310121641 A CN201310121641 A CN 201310121641A CN 104098517 A CN104098517 A CN 104098517A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention relates to a lapatinib intermediate preparation method, the lapatinib intermediate is shown as the formula I shown in the specification, the route of the lapatinib intermediate preparation method is shown in the specification, the lapatinib intermediate preparation method is simple and safe in operation, good in yield, less in pollution to the environment, very good in economic effect, and suitable for industrial production. R is selected from Br, I and 5-((N tert butoxycarbonyl-2-((methyl sulfonyl) ethyl) amino) methyl) furan-2-yl and 5-aldehyde furan-2-yl.
Description
Technical field
The present invention relates to a kind of method of preparing lapatinib intermediate.
Technical background
Lapatinibditosylate is produced by GlaxoSmithKline PLC, is a kind of oral small molecules Urogastron tyrosine kinase inhibitor.Be mainly used in associating capecitabine treatment ErbB-2 overexpression, previously accepted to comprise anthracycline, taxol, late period or the metastatic breast cancer of Herceptin (Trastuzumab) treatment.
Lapatinibditosylate has the report of several different patent routes:
1) WO 1999035146 reports following preparation method:
2) WO2010061400 reports following preparation method:
3) WO 2011039759 reports following preparation method:
4) CN 102702178 reports following preparation method:
As can be seen here, all there is complex steps in existing lapatinibditosylate synthetic route, and raw material and reagent cost are high, and the weak points such as the invisible production cost also increasing of protecting group are gone in protection.Therefore, develop the synthetic method of new lapatinib intermediate, to overcome the defect of prior art, tool is of great significance.
Summary of the invention
The present invention has been intended to invent a kind of new synthetic method and has prepared lapatinib intermediate, and the method is with low cost, safety simple to operation, and yield is good, and environmental pollution is simultaneously little, has good economic benefits, suitable industrial production.
The method is summarized as follows:
Wherein R takes from Br, I, 5-((N-tertbutyloxycarbonyl-(2-(methyl sulphonyl) ethyl) amino) methyl) furans-2-base and 5-aldehyde radical furans-2-base.
Its concrete operation step is:
Under the effect of alkali, react preparationⅠcompound with formula III by making formula II;
Alkali can be organic bases or mineral alkali, preferably mineral alkali, and mineral alkali can be selected from salt of wormwood or sodium carbonate, potassium hydroxide or sodium hydroxide; Reaction is selected from C
3-6ketone or C
3-8acid amides or C
1-8alcohol or C
2-8ether or C
1-8in the mixture of nitrile and water, carry out C
3-6the preferred acetone of ketone, butanone, C
3-8the preferred DMF of acid amides, N,N-dimethylacetamide, C
1-8alcohol particular methanol, ethanol, Virahol, C
2-8the preferred tetrahydrofuran (THF) of ether, ether, glycol dimethyl ether, dioxane, C
1-8the preferred acetonitrile of nitrile, more preferably in the mixed solvent of DMF and water, react; Temperature of reaction is selected from-20 DEG C-110 DEG C, preferably-10 DEG C-30 DEG C.
The invention provides formula II compound and preparation method thereof, the method comprises through type IV and formula V reaction preparation formula II compound;
Reaction formula is as follows:
Wherein R takes from Br, I, 5-((N-tertbutyloxycarbonyl-(2-(methyl sulphonyl) ethyl) amino) methyl) furans-2-base and 5-aldehyde radical furans-2-base.
Reaction is selected from C
3-6ketone or C
3-8acid amides or C
1-8alcohol or C
2-8ether or C
1-8nitrile or C
6-9in aromatic hydrocarbon, carry out C
3-6the preferred butanone of ketone, C
3-8the preferred DMF of acid amides, N,N-dimethylacetamide, C
1-8the preferred Virahol of alcohol, the trimethyl carbinol, C
2-8the preferred tetrahydrofuran (THF) of ether, ether, glycol dimethyl ether, dioxane, C
1-8the preferred acetonitrile of nitrile, C
6-9the preferred toluene of aromatic hydrocarbon, dimethylbenzene, more preferably in Virahol or acetonitrile solvent, react; Temperature of reaction is selected from 0 DEG C-110 DEG C, is preferable over 60 DEG C-90 DEG C.
The invention provides compound of a kind of formula VII and preparation method thereof:
The method comprises through type VI compound and formula V compound preparation formula VII compound;
Reaction formula is as follows:
Reaction is selected from C
3-6ketone or C
3-8acid amides or C
1-8alcohol or C
2-8ether or C
1-8nitrile or C
6-9in aromatic hydrocarbon solvent, carry out C
3-6the preferred butanone of ketone, C
3-8the preferred DMF of acid amides, N,N-dimethylacetamide, C
1-8the preferred Virahol of alcohol, the trimethyl carbinol, C
2-8the preferred tetrahydrofuran (THF) of ether, ether, glycol dimethyl ether, dioxane, C
1-8the preferred acetonitrile of nitrile, C
6-9the preferred toluene of aromatic hydrocarbon, dimethylbenzene, more preferably in Virahol or acetonitrile solvent, react; Temperature of reaction is selected from 0 DEG C-110 DEG C, 60 DEG C-90 DEG C of preferable reaction temperature.
The invention provides compound of a kind of formula IX and preparation method thereof, also provide this intermediate and a fluorine bromobenzyl to carry out a step condensation, then with 2-(methylsulfonyl) ethamine reduction amination obtains lapatinibditosylate.
The method comprises through type VII compound and formula VIII compound preparation formula IX compound under alkali and catalyst action;
Reaction formula is as follows:
Catalyzer is selected from palladium catalyst, the preferred palladium carbon of palladium catalyst, Palladous chloride, palladium, tetra-triphenylphosphine palladium, two (triphenylphosphine) palladium chloride, 1,1 '-bis-(diphenylphosphine) ferrocene palladium chloride methylene dichloride complex compound, more preferred two (triphenylphosphine) palladium chloride (Pd(PDDD)
2cl
2); Alkali is selected from organic bases or mineral alkali, the preferred salt of wormwood of mineral alkali or sodium carbonate, the preferred triethylamine of organic bases; Reaction is selected from C
3-8acid amides or C
2-8ether or C
3-8in the single solvent of ester or alcohol or water or any two kinds of mixtures, carry out C
3-8the preferred DMF of acid amides, N,N-dimethylacetamide, C
2-8the preferred tetrahydrofuran (THF) of ether, glycol dimethyl ether, dioxane, C
3-8ester ethyl acetate, C
1-8alcohol particular methanol, ethanol, more preferably in dioxane and water mixed solvent, carry out; Temperature of reaction is selected from 0 DEG C-100 DEG C, 40 DEG C-70 DEG C of preferable reaction temperature.
Embodiment
Following examples illustrate the present invention, but and unrestricted the present invention.
Synthesizing of example 1 N-(the chloro-4-of 3-(3-luorobenzyl oxygen base) phenyl)-6-bromine quinazoline-4-amine:
Method 1) add successively DMF(24ml in 100ml four-hole bottle), water 6ml, salt of wormwood (2.26g, 16.38mmol) N-(the chloro-4 – hydroxy phenyls of 3-)-6-bromine quinazoline-4-amine hydrochlorate (2.1g, 5.46mmol), be cooled to 0 DEG C, fluorine bromobenzyl (1.03g, 5.45mmol) between dropping.Drip and finish, at 0 DEG C, stir 18h.React complete, add water (50ml), suction filtration, ethanol for filter cake (10ml) making beating, suction filtration, filter cake is dried in 45 DEG C of convection oven, obtains yellow solid (2.2g, yield 88%):
LC-MS:460[M+1]
+
Method 2) add successively ethanol (24ml) in 100ml four-hole bottle, water 6ml, salt of wormwood (2.26g, 16.38mmol) N-(the chloro-4 – hydroxy phenyls of 3-)-6-bromine quinazoline-4-amine hydrochlorate (2.1g, 5.46mmol), be cooled to 0 DEG C, fluorine bromobenzyl (1.03g, 5.45mmol) between dropping.Drip and finish, at 0 DEG C, stir 18h.React complete, add water (50ml), suction filtration, ethanol for filter cake (10ml) making beating, suction filtration, filter cake is dried in 45 DEG C of convection oven, obtains yellow solid (2.1g, yield 84%).
Synthesizing of example 2 N-(the chloro-4-of 3-(3-luorobenzyl oxygen base) phenyl)-6-iodine quinazoline-4-amine:
Method 1) add successively acetone (24ml) in 100ml four-hole bottle, water 6ml, sodium carbonate (1.74g, 16.38mmol) N-(the chloro-4 – hydroxy phenyls of 3-)-6-iodine quinazoline-4-amine hydrochlorate (2.37g, 5.46mmol), be cooled to 0 DEG C, fluorine bromobenzyl (1.03g, 5.45mmol) between dropping.Drip and finish, at 0 DEG C, stir 18h.React complete, add water (50ml), suction filtration, ethanol for filter cake (10ml) making beating, suction filtration, filter cake is dried in 45 DEG C of convection oven, obtains brown solid (2.5g, yield 91%): LC-MS:506[M+1]
+
Method 2) add successively acetonitrile (24ml) in 100ml four-hole bottle, water 6ml, salt of wormwood (2.26g, 16.38mmol) N-(the chloro-4 – hydroxy phenyls of 3-)-6-iodine quinazoline-4-amine hydrochlorate (2.37g, 5.46mmol), be cooled to 0 DEG C, fluorine bromobenzyl (1.03g, 5.45mmol) between dropping.Drip and finish, at 0 DEG C, stir 18h.React complete, add water (50ml), suction filtration, ethanol for filter cake (10ml) making beating, suction filtration, filter cake is dried in 45 DEG C of convection oven, obtains brown solid (2.4g, yield 87%).
Synthesizing of example 3 5-(4-(the chloro-4-of 3-(3-fluorine benzyloxy) phenyl amino) quinazoline-6-yl) furans-2-formaldehyde:
In 100ml four-hole bottle, add successively DMF(24ml), water 6ml, salt of wormwood (1.5g, 10.87mmol) 5-(4-(3-chloro-4-hydroxyl phenylamino) quinazoline-6-yl) furans-2-formaldehyde (2g, 5.46mmol), be cooled to 0 DEG C, fluorine bromobenzyl (1.03g, 5.45mmol) between dropping.Drip and finish, at 0 DEG C, stir 18h.React complete, add water (50ml), suction filtration, ethanol for filter cake (10ml) making beating, suction filtration, filter cake is dried in 45 DEG C of convection oven, obtains yellow solid (2.3g, yield 90%): LC-MS:474[M+1]
+,
1hNMR(DMSO-d
6): δ 5.20(s, 2H), 7.17(m, 1H) and, 7.29(m, 3H), 7.41(m, 2H), 7.74(m, 2H), 7.86(d, J=9.0Hz, 1H), 7.97(s, 1H), 8.31(d, J=9.0Hz, 1H), 8.56(s, 1H), 8.96(s, 1H), 9.66(s, 1H), 10.11(s, 1H).
Example 4 N-(the chloro-4-of 3-(3-luorobenzyl oxygen base) phenyl)-6-(5-((N-tertbutyloxycarbonyl-2-((methyl sulphonyl) ethyl) amino) methyl) furans-2-yl) quinazoline-4-amine synthetic:
In 100ml four-hole bottle, add successively DMF(24ml); water 6ml; salt of wormwood (1.5g; 10.87mmol) N-(the chloro-4 – hydroxy phenyls of 3-)-6-(5-((N-tertbutyloxycarbonyl-(2-(methyl sulphonyl) ethyl) amino) methyl) furans-2-yl) quinazoline-4-amine (3.1g; 5.46mmol); be cooled to 0 DEG C, fluorine bromobenzyl (1.03g, 5.45mmol) between dropping.Drip and finish, at 0 DEG C, stir 18h.React complete, add water (50ml), suction filtration, ethanol for filter cake (10ml) making beating, suction filtration, filter cake is dried in 45 DEG C of convection oven, obtains yellow solid (3.5g, yield 94%): LC-MS:681[M+1]
+
Example 5 4-(6-bromine quinazoline-4-base amino)-2-chlorophenol synthetic:
Method 1) add successively acetonitrile (600ml) to 1L four-hole bottle, the chloro-PAP of 2-(32.8g, 228.45mmol), then add 6-bromo-4-chloro-quinazoline hydrochloride (64g, 228.45mmol), be warming up to 80 DEG C of backflow 3h.Reaction is finished, and is cooled to stirring at room temperature 2h, and suction filtration obtains yellow solid (86g, 97%).LC-MS:352[M+1]
+，
1HNMR（DMSO-d
6）：δ7.10（d，J=8.8Hz，1H），7.50（m，1H），7.78（s，1H），7.90（d，J=8.8Hz，1H），8.20（d，J=8.8Hz，1H），8.94（s，1H），9.22（s，1H），10.61（s，1H），11.71（s，1H）。
Method 2) add successively Virahol (600ml) to 1L four-hole bottle, the chloro-PAP of 2-(32.8g, 228.45mmol), then add 6-bromo-4-chloro-quinazoline hydrochloride (64g, 228.45mmol), be warming up to 82 DEG C of backflow 3h.Reaction is finished, and is cooled to stirring at room temperature 2h, and suction filtration obtains yellow solid (88g, 99.5%).
Method 3) add successively THF(600ml to 1L four-hole bottle), the chloro-PAP of 2-(32.8g, 228.45mmol), then add 6-bromo-4-chloro-quinazoline hydrochloride (64g, 228.45mmol), be warming up to 66 DEG C of backflow 3h.Reaction is finished, and is cooled to stirring at room temperature 2h, and suction filtration obtains yellow solid (83g, 95%).
Method 4) add successively DMF(600ml to 1L four-hole bottle), the chloro-PAP of 2-(32.8g, 228.45mmol), then add 6-bromo-4-chloro-quinazoline hydrochloride (64g, 228.45mmol), be warming up to 80 DEG C of insulation 3h.Reaction is finished, and is cooled to room temperature, drips 600ml water, stirs 2h, and suction filtration obtains yellow solid (75g, 85%).
Implement 6 5-(4-(3-chloro-4-hydroxyl phenylaminos) quinazoline-6-yl) furans-2-formaldehyde synthetic:
Method 1) under nitrogen protection, add successively dioxane (48ml) to 100ml four-hole bottle, water (12ml); 4-(6-bromine quinazoline-4-base amino)-2-chlorophenol (6g, 17.1mmol), 5-aldehyde radical FURAN-2-BORONIC ACID (4.8g; 34.3mmol), salt of wormwood (6.0g43.5mmol).After nitrogen deoxygenation 30 minutes, then add Pd(PDDD)
2cl
2, (0.3g, 5%), is warming up to 50 DEG C of insulation 24h.Reaction is finished, and is cooled to room temperature, adds water (100ml), stirs 2h, suction filtration.Methyl alcohol for filter cake (100ml) rising temperature for dissolving, filtered while hot.Filtrate is cooled to room temperature, drips water (200ml), stirs 2h, and suction filtration obtains yellow solid (5.2g, 83%).LC-MS:366[M+1]
+，
1HNMR（DMSO-d
6）：δ7.01（d，J=8.8Hz，1H），7.42（d，J=3.6Hz，1H），7.51（dd，J=2.4Hz，J=8.8Hz，1H），7.75（d，J=8.8Hz，1H），7.83（m，1H），7.86（s，1H），8.29（dd，J=1.6Hz，J=8.8Hz，1H），8.56（s，1H），8.99（s，1H），9.67（s，1H），10.09（s，1H），10.14（s，1H）。
Method 2) under nitrogen protection, add successively DMF(60ml to 100ml four-hole bottle), 4-(6-bromine quinazoline-4-base amino)-2-chlorophenol (6g; 17.1mmol); 5-aldehyde radical FURAN-2-BORONIC ACID (4.8g, 34.3mmol), triethylamine (4.4g43.5mmol).After nitrogen deoxygenation 30 minutes, then add tetra-triphenylphosphine palladium (0.3g, 5%), be warming up to 60 DEG C of insulation 24h.Reaction is finished, and is cooled to room temperature, adds water (100ml), stirs 2h, suction filtration.Methyl alcohol for filter cake (100ml) rising temperature for dissolving, filtered while hot.Filtrate is cooled to room temperature, drips water (200ml), stirs 2h, and suction filtration obtains yellow solid (4.9g, 78%).
Method 3) under nitrogen protection, add successively ethyl acetate (40ml), DMF(20ml to 100ml four-hole bottle) 4-(6-bromine quinoxaline-4-base amino)-2-chlorophenol (6g; 17.1mmol); 5-aldehyde radical FURAN-2-BORONIC ACID (4.8g, 34.3mmol), salt of wormwood (6.0g43.5mmol).After nitrogen deoxygenation 30 minutes, then add palladium (0.3g, 5%), be warming up to 80 DEG C of insulation 24h.Reaction is finished, and is cooled to room temperature, adds water (100ml), stirs 2h, suction filtration.Methyl alcohol for filter cake (100ml) rising temperature for dissolving, filtered while hot.Filtrate is cooled to room temperature, drips water (200ml), stirs 2h, and suction filtration obtains yellow solid (4.7g, 75%).
Method 4) under nitrogen protection, add successively THF(40ml to 100ml four-hole bottle), MeOH(20ml) 4-(6-bromine quinazoline-4-base amino)-2-chlorophenol (6g; 17.1mmol); 5-aldehyde radical FURAN-2-BORONIC ACID (4.8g, 34.3mmol), salt of wormwood (6.0g43.5mmol).After nitrogen deoxygenation 30 minutes, then add palladium chloride (0.3g, 5%), be warming up to 60 DEG C of insulation 24h.Reaction is finished, and is cooled to room temperature, adds water (100ml), stirs 2h, suction filtration.Methyl alcohol for filter cake (100ml) rising temperature for dissolving, filtered while hot.Filtrate is cooled to room temperature, drips water (200ml), stirs 2h, and suction filtration obtains yellow solid (4.4g, 70%).
Claims (10)
1. a method for preparation formula I, by making formula II react and prepare under the effect of organic bases or mineral alkali with formula III, reaction formula is as follows:
Wherein R takes from Br, I, 5-((N-tertbutyloxycarbonyl-(2-(methyl sulphonyl) ethyl) amino) methyl) furans-2-base and 5-aldehyde radical furans-2-base.
2. method according to claim 1, is characterized in that described mineral alkali is selected from salt of wormwood, sodium carbonate, potassium hydroxide or sodium hydroxide.
3. method according to claim 1, is characterized in that reaction is at C
3-6ketone or C
3-8acid amides or C
1-8alcohol or C
2-8ether or C
1-8in the mixture of nitrile and water, carry out, wherein C
3-6the preferred acetone of ketone or butanone; C
3-8the preferred DMF of acid amides or N,N-dimethylacetamide; C
1-8alcohol particular methanol, ethanol or Virahol; C
2-8the preferred tetrahydrofuran (THF) of ether, ether, glycol dimethyl ether or dioxane; C
1-8the preferred acetonitrile of nitrile; Reaction is further preferably reacted in the mixed solvent of DMF and water.
4. method according to claim 1, is characterized in that ,-20 DEG C of-110 DEG C of reactions, preferable reaction temperature is-10 DEG C-30 DEG C.
5. prepare a method for the II of formula described in claim 1 compound, through type IV and formula V reaction preparation formula II compound, reaction formula is as follows:
Wherein R takes from Br, I, 5-((N-tertbutyloxycarbonyl-(2-(methyl sulphonyl) ethyl) amino) methyl) furans-2-base and 5-aldehyde radical furans-2-base.
6. method according to claim 5, is characterized in that reaction is at C
3-6ketone or C
3-8acid amides or C
1-8alcohol or C
2-8ether or C
1-8nitrile or C
6-9in aromatic hydrocarbon, carry out; Wherein C
3-6the preferred butanone of ketone; C
3-8the preferred DMF of acid amides or N,N-dimethylacetamide; C
1-8the preferred Virahol of alcohol or the trimethyl carbinol; C
2-8the preferred tetrahydrofuran (THF) of ether, ether, glycol dimethyl ether or dioxane; C
1-8the preferred acetonitrile of nitrile; C
6-9the preferred toluene of aromatic hydrocarbon or dimethylbenzene; Reaction is further preferably reacted in Virahol or acetonitrile solvent; Temperature of reaction is selected from 0 DEG C-110 DEG C, and preferable reaction temperature is 60 DEG C-90 DEG C.
7. formula VII and formula IX compound:
8. a method of preparing formula IX compound described in claim 7, comprises following steps:
1) through type VI compound and formula V compound or its salt preparation formula VII compound;
2) formula VII compound and formula VIII compound prepare formula IX compound under organic bases or mineral alkali and catalyst action, and reaction formula is as follows:
9. method according to claim 8, is characterized in that described step 1) reaction is selected from C
3-6ketone or C
3-8acid amides or C
1-8alcohol or C
2-8ether or C
1-8nitrile or C
6-9in aromatic hydrocarbon solvent, carry out; Wherein C
3-6the preferred butanone of ketone, C
3-8the preferred DMF of acid amides or N,N-dimethylacetamide; C
1-8the preferred Virahol of alcohol or the trimethyl carbinol; C
2-8the preferred tetrahydrofuran (THF) of ether, ether, glycol dimethyl ether or dioxane; C
1-8the preferred acetonitrile of nitrile; C
6-9the preferred toluene of aromatic hydrocarbon or dimethylbenzene, reaction is further carried out in Virahol or acetonitrile solvent; Temperature of reaction is selected from 0 DEG C-110 DEG C, and preferable reaction temperature is 60 DEG C-90 DEG C.
10. method according to claim 8, it is characterized in that described step 2) catalyzer is selected from palladium catalyst, the preferred palladium carbon of palladium catalyst, Palladous chloride, palladium, tetra-triphenylphosphine palladium, two (triphenylphosphine) palladium chloride or 1,1 '-bis-(diphenylphosphine) ferrocene palladium chloride methylene dichloride complex compound, further preferred two (triphenylphosphine) palladium chloride; Mineral alkali is selected from salt of wormwood or sodium carbonate, and organic bases is selected from triethylamine; Reaction is selected from C
3-8acid amides or C
2-8ether or C
3-8in the single solvent of ester or alcohol or water or any two kinds of mixtures, carry out C
3-8the preferred DMF of acid amides or N,N-dimethylacetamide, C
2-8the preferred tetrahydrofuran (THF) of ether, glycol dimethyl ether or dioxane, C
3-8ester ethyl acetate, C
1-8alcohol particular methanol or ethanol further preferably react in dioxane and water mixed solvent; Temperature of reaction is selected from 0 DEG C-100 DEG C, is preferable over 40 DEG C-70 DEG C.
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| CN201310121641.8A CN104098517A (en) | 2013-04-09 | 2013-04-09 | Lapatinib intermediate preparation method |
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| CN201310121641.8A CN104098517A (en) | 2013-04-09 | 2013-04-09 | Lapatinib intermediate preparation method |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7157466B2 (en) * | 2000-06-30 | 2007-01-02 | Smithkline Beecham (Cork) Limited | Quinazoline ditosylate salt compounds |
| CN102079759A (en) * | 2009-12-01 | 2011-06-01 | 天津药物研究院 | 6-substituted quinazoline derivative, preparation method and application thereof |
| CN102675297A (en) * | 2012-04-17 | 2012-09-19 | 武汉人福医药集团股份有限公司 | Preparation method of Lapatinib |
| CN102911164A (en) * | 2012-11-07 | 2013-02-06 | 江苏金桥盐化集团利海化工有限公司 | Method for preparing lapatinib key intermediate |
-
2013
- 2013-04-09 CN CN201310121641.8A patent/CN104098517A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7157466B2 (en) * | 2000-06-30 | 2007-01-02 | Smithkline Beecham (Cork) Limited | Quinazoline ditosylate salt compounds |
| CN102079759A (en) * | 2009-12-01 | 2011-06-01 | 天津药物研究院 | 6-substituted quinazoline derivative, preparation method and application thereof |
| CN102675297A (en) * | 2012-04-17 | 2012-09-19 | 武汉人福医药集团股份有限公司 | Preparation method of Lapatinib |
| CN102911164A (en) * | 2012-11-07 | 2013-02-06 | 江苏金桥盐化集团利海化工有限公司 | Method for preparing lapatinib key intermediate |
Non-Patent Citations (1)
| Title |
|---|
| FALGUNI BASULI ET AL: "A first synthesis of 18F‐radiolabeled lapatinib: a potential tracer for positron emission tomographic imaging of ErbB1/ErbB2 tyrosine kinase activity", 《JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS》 * |
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