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N-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺 | 162012-67-1

物质功能分类

医药中间体 - 原料药中间体

分子结构分类

有机化合物 - 有机杂环化合物 - 二氮杂萘

中文名称

N-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺

中文别名

4-(3-氯-4-氟苯基氨基)-7-氟-6-硝基喹唑啉；4-(3-氯-4-氟苯胺)7-甲氧基-喹唑啉-6-硝基胺；卡那替尼中间体2；N-(3-氯-4氟苯基)-7-氟-6-硝基喹唑啉胺；4-[(3-氯-4-氟)氨基]-6-硝基-7-氟-喹唑啉氨；阿法中间体2；N-(3-氯-4-氟苯基)-7-氟-6-硝基喹唑啉-4-胺；N-4-(3-氯-4-氟苯基)-7-氟-6-硝基-4-氨基-喹唑啉

英文名称

N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

英文别名

N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine；4-(3-chloro-4-fluorophenyl)amino-6-nitro-7-fluoroquinazoline；(3-Chloro-4-fluoro-phenyl)-(7-fluoro-6-nitro-quinazolin-4-yl)-amine

CAS

162012-67-1

化学式

C₁₄H₇ClF₂N₄O₂

mdl

——

分子量

336.685

InChiKey

CJOJDNRJDBWZKM-UHFFFAOYSA-N

BEILSTEIN

——

EINECS

——

物化性质

熔点：

242-244℃
沸点：

489℃
密度：

1.616
闪点：

249℃
溶解度：

DMSO（微溶）、甲醇（微溶、超声处理）

计算性质

辛醇/水分配系数(LogP)：

4.1
重原子数：

23
可旋转键数：

2
环数：

3.0
sp3杂化的碳原子比例：

0.0
拓扑面积：

83.6
氢给体数：

1
氢受体数：

7

安全信息

海关编码：

2933990090
危险性防范说明：

P305+P351+P338
危险性描述：

H315,H319
储存条件：

储存条件：室温、密封保存，并置于干燥处。

SDS

SDS：f18957e7e55f9150685075da65237549

查看

制备方法与用途

用途

N-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺是合成阿法替尼的重要中间体。阿法替尼是一种用于治疗呼吸道、肺部的癌症和疾病，以及胃肠道、胆管和胆囊疾病的氨基巴豆酰氨基取代的喹唑啉衍生物。

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
4-氯-7-氟-6-硝基喹唑啉	4-chloro-7-fluoro-6-nitroquinazoline	162012-70-6	C₈H₃ClFN₃O₂	227.582
7-氟-6-硝基-4-羟基喹唑啉	7-fluoro-6-nitro-3H-quinazolin-4-one	162012-69-3	C₈H₄FN₃O₃	209.136

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	4-(3'-chloro-4'-fluoroanilino)-7-fluoro-6-hydroxyaminoquinazoline	——	C₁₄H₉ClF₂N₄O	322.701
——	N-(3-chloro-4-fluorophenyl)-7-fluoro-6-amino-4-quinazolinamine	——	C₁₄H₉ClF₂N₄	306.702
——	4-((3-chloro-4-fluorophenyl)amino)-6-nitroquinazolin-7-ol	——	C₁₄H₈ClFN₄O₃	334.694
N-(3-氯-4-氟苯基)-7-甲氧基-6-硝基喹唑啉-4-胺	N-(3-chloro-4-fluorophenyl)-7-methoxy-6-nitroquinazolin-4-amine	179552-74-0	C₁₅H₁₀ClFN₄O₃	348.721
——	7-(2-aminoethoxy)-N-(3-chloro-4-fluorophenyl)-6-nitro-4-quinazolinamine	936558-11-1	C₁₆H₁₃ClFN₅O₃	377.762
——	7-(2-fluoroethoxy)-6-nitro-4-(3-chloro-4-fluoroaniline)quinazoline	869199-53-1	C₁₆H₁₁ClF₂N₄O₃	380.738
——	N-(3-chloro-4-fluorophenyl)-7-(2-methoxyethoxy)-6-nitroquinazolin-4-amine	402855-06-5	C₁₇H₁₄ClFN₄O₄	392.774
——	N-(3-chloro-4-fluorophenyl)-6-nitro-7-(prop-2-yn-1-yloxy)quinazolin-4-amine	——	C₁₇H₁₀ClFN₄O₃	372.743
——	(3-Chloro-4-fluoro-phenyl)-[7-(2,2-difluoro-ethoxy)-6-nitro-quinazolin-4-yl]-amine	869199-63-3	C₁₆H₁₀ClF₃N₄O₃	398.729
4-[(3-氯-4-氟-苯基)氨基]-7-环丙基甲氧基-6-硝基-喹唑啉	4-[(3-chloro-4-fluoro-phenyl)amino]-7-cyclopropylmethoxy-6-nitro-quinazoline	290303-52-5	C₁₈H₁₄ClFN₄O₃	388.786
N-（3-氯-4-氟苯基）-7-甲氧基-6-氨基喹唑啉-4-胺	N⁴-(3-chloro-4-fluorophenyl)-7-methoxyquinazoline-4,6-diamine	179552-75-1	C₁₅H₁₂ClFN₄O	318.738
——	N-(3-chloro-4-fluorophenyl)-6-nitro-7-(3-(piperazin-1-yl)propoxy)quinazolin-4-amine	——	C₂₁H₂₂ClFN₆O₃	460.895
——	2-(4-(3-chloro-4-fluorophenylamino)-6-nitro-quinazolin-7-oxy)ethyl tert-butylcarbamate	936558-10-0	C₂₁H₂₁ClFN₅O₅	477.88
N-(3-氯-4-氟苯基)-7-(3-吗啉丙氧基)-6-硝基喹唑啉-4-胺	4-[N-(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline	267243-64-1	C₂₁H₂₁ClFN₅O₄	461.88
——	4-[(3-chloro-4-fluoro-phenyl)amino]-7-[3-(tetrahydropyran-2-yloxy)-propyloxy]-6-nitro-quinazoline	——	C₂₂H₂₂ClFN₄O₅	476.892
——	4-[(3-chloro-4-fluoro-phenyl)amino]-7-[2-(tetrahydropyran-2-yloxy)-ethoxy]-6-nitro-quinazoline	——	C₂₁H₂₀ClFN₄O₅	462.865
N-(3-氯-4-氟苯基)-6-硝基-7-[[(3S)-四氢-3-呋喃基]氧基]-4-喹唑啉胺	4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline	314771-88-5	C₁₈H₁₄ClFN₄O₄	404.785
——	4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-(5-tetrahydrofuran-3-yloxy)quinazoline	——	C₁₈H₁₄ClFN₄O₄	404.785
——	N⁴-(3-chloro-4-fluorophenyl)-7-ethoxyquinazoline-4,6-diamine	1269662-90-9	C₁₆H₁₄ClFN₄O	332.765
——	N-(4-(3-chloro-4-fluorophenyl))-7-((spiro[3.5]octan-2-yl)methoxy)-6-nitroquinazolin-4-amine	1363359-90-3	C₂₄H₂₄ClFN₄O₃	470.931
——	7-(bicyclo[3.1.0]hexan-6-ylmethoxy)-N-(4-(3-chloro-4-fluorophenyl))-6-nitroquinazolin-4-amine	1363359-92-5	C₂₁H₁₈ClFN₄O₃	428.85
——	7-(3-oxabicyclo[3.1.0]hexan-6-ylmethoxy)-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine	1412452-20-0	C₂₀H₁₆ClFN₄O₄	430.823
——	N⁴-(3-chloro-4-fluorophenyl)-7-(prop-2-yn-1-yloxy)quinazoline-4,6-diamine	——	C₁₇H₁₂ClFN₄O	342.76
N4-(3-氯-4-氟苯基)-7-(2-甲氧基乙氧基)-4,6-喹唑啉二胺	N⁴-(3-chloro-4-fluorophenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine	402855-01-0	C₁₇H₁₆ClFN₄O₂	362.791
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(7-methyl-7-azaspiro[3.5]nonan-2-yl)ethoxy)-6-nitroquinazolin-4-amine	1363359-85-6	C₂₅H₂₇ClFN₅O₃	499.972
——	N-(3-chloro-4-fluorophenyl)-7-((7-methyl-7-azaspiro[3.5]nonan-2-yl)methoxy)-6-nitroquinazolin-4-amine	1363359-83-4	C₂₄H₂₅ClFN₅O₃	485.946
——	7-(8-oxabicyclo[3.2.1]octan-3-yloxy)-N-(4-(3-chloro-4-fluorophenyl))-6-nitroquinazolin-4-amine	1363359-55-0	C₂₁H₁₈ClFN₄O₄	444.85
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(6-methyl-6-azaspiro[2.5]octan-1-yl)ethoxy)-6-nitroquinazolin-4-amine	1363359-81-2	C₂₄H₂₅ClFN₅O₃	485.946
——	N-(3-chloro-4-fluorophenyl)-7-(2-((1R,5S,6S)-3-methyl-3-azabicyclo[3.1.0]hexan-6-yl)ethoxy)-6-nitroquinazolin-4-amine	1363359-69-6	C₂₂H₂₁ClFN₅O₃	457.892
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(3-methyl-3-azabicyclo[3.1.0]-6-hexyl)-ethoxy)-6-nitroquinazolin-4-amine	1363359-88-9	C₂₂H₂₁ClFN₅O₃	457.892
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(3-methyl-3-azabicyclo[3.2.1]octan-8-yl)ethoxy)-6-nitroquinazolin-4-amine	——	C₂₄H₂₅ClFN₅O₃	485.946
——	N-(4-(3-chloro-4-fluorophenyl))-7-((6-methyl-6-azaspiro[2.5]octan-1-yl)methoxy)-6-nitro quinazolin-4-amine	1363359-79-8	C₂₃H₂₃ClFN₅O₃	471.919
——	tert-butyl 4-(3-((4-((3-chloro-4-fluorophenyl)amino)-6-nitroquinazolin-7-yl) oxy)propyl)piperazine-1-carboxylate	——	C₂₆H₃₀ClFN₆O₅	561.013
——	8-(6-amino-4-(3-chloro-4-fluoroanilino)quinazoline-7-yloxy)octanoic acid	——	C₂₂H₂₄ClFN₄O₃	446.909
——	N-(4-(3-chloro-4-fluorophenyl))-7-(8-methyl-8-azabicyclo[3.2.1]octan-3-yloxy)-6-nitroquinazolin-4-amine	1363359-61-8	C₂₂H₂₁ClFN₅O₃	457.892
——	N-(3-chloro-4-fluorophenyl)-7,8-dihydro-6H-[1,4]oxazino[3,2-g]quinazolin-4-amine	——	C₁₆H₁₂ClFN₄O	330.749
——	N-(3-chloro-4-fluorophenyl)-6-nitro-7-(3-D-tetrahydrafuran-3-yloxy)qunazolin-4-amine	1357358-20-3	C₁₈H₁₄ClFN₄O₄	405.777
——	7-(7-oxabicyclo[2.2.1]heptan-2-yloxy)-N-(4-(3-chloro-4-fluorophenyl))-6-nitroquinazolin-4-amine	1363359-57-2	C₂₀H₁₆ClFN₄O₄	430.823
N4-(3-氯-4-氟苯基)-7-[[(3S)-四氢-3-呋喃基]氧基]-4,6-喹唑啉二胺	4-[(3-chloro-4-fluorophenyl)amino]-6-amino-7-((S)-tetrahydrofuran-3-yloxy)quinazoline	314771-76-1	C₁₈H₁₆ClFN₄O₂	374.802
——	N-(3-chloro-4-fluorophenyl)-6-amino-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine	——	C₁₈H₁₆ClFN₄O₂	374.802
——	N-(4-(3-chloro-4-fluorophenyl))-7-((5-methyl-5-azaspiro[2.4]heptan-1-yl)methoxy)-6-nitroquinazolin-4-amine	1363359-77-6	C₂₂H₂₁ClFN₅O₃	457.892
N4-(3-氯-4-氟苯基)-7-(3-吗啉丙氧基)喹唑啉-4,6-二胺	6-amino-4-[N-(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazoline	267243-68-5	C₂₁H₂₃ClFN₅O₂	431.897
——	N-(4-(3-chloro-4-fluorophenyl))-7-((spiro[3.5]octan-2-yl)methoxy)-quinazolin-4,6-diamine	1363359-91-4	C₂₄H₂₆ClFN₄O	440.948
——	N-(4-(3-chloro-4-fluorophenyl))-7-(8-methyl-1-oxa-8-azaspiro[4.5]decan-2-ylmethoxy)-6-nitroquinazolin-4-amine	1363359-67-4	C₂₄H₂₅ClFN₅O₄	501.945
——	N-(4-(3-chloro-4-fluorophenyl))-7-((8-methyl-1-oxa-8-azaspiro[4.5]decan-3-yl)methoxy)-6-nitroquinazolin-4-amine	1363359-65-2	C₂₄H₂₅ClFN₅O₄	501.945
——	N-(4-(3-chloro-4-fluorophenyl))-7-((7-methyl-7-azabicyclo[2.2.1]heptan-2-yl)methoxy)-6-nitroquinazolin-4-amine	1363359-73-2	C₂₂H₂₁ClFN₅O₃	457.892
——	7-(bicyclo[3.1.0]hexan-6-ylmethoxy)-N-(4-(3-chloro-4-fluorophenyl))quinazolin-4,6-diamine	1363359-93-6	C₂₁H₂₀ClFN₄O	398.867
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-methyl-2,7-diazaspiro[4.5]decan-7-yl)-6-nitroquinazolin-4-amine	1363359-59-4	C₂₃H₂₄ClFN₆O₂	470.934
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(7-methyl-7-azaspiro[3.5]nonan-2-yl)ethoxy)quinazolin-4,6-diamine	1363359-86-7	C₂₅H₂₉ClFN₅O	469.99
——	7-(8-oxabicyclo[3.2.1]octan-3-yloxy)-N-(4-(3-chloro-4-fluorophenyl))quinazolin-4,6-diamine	1363359-56-1	C₂₁H₂₀ClFN₄O₂	414.867
——	N-(4-(3-chloro-4-fluorophenyl))-7-((7-methyl-7-azaspiro[3.5]nonan-2-yl)methoxy)quinazolin-4,6-diamine	1363359-84-5	C₂₄H₂₇ClFN₅O	455.963
——	N-(3-chloro-4-fluorophenyl)-7-(((3S,3aS,6R,6aS)-6-methoxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-6-nitroquinazolin-4-amine	——	C₂₁H₁₈ClFN₄O₆	476.849
——	(E)-4-bromo-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)but-2-enamide	1245555-80-9	C₁₉H₁₅BrClFN₄O₂	465.709
——	N-(4-((3-chloro-4-fluorophenyl)amino)-7-(prop-2-yn-1-yloxy)quinazolin-6-yl)acrylamide	1621002-23-0	C₂₀H₁₄ClFN₄O₂	396.808
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(6-methyl-6-azaspiro[2.5]octan-1-yl)ethoxy)quinazolin-4,6-diamine	1363359-82-3	C₂₄H₂₇ClFN₅O	455.963
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(3-methyl-3-aza-bicyclo[3.1.0]-6-hexyl)-ethoxy)quinazolin-4,6-diamine	1363359-89-0	C₂₂H₂₃ClFN₅O	427.909
——	N4-(3-chloro-4-fluorophenyl)-7-(2-((1R,5S,6S)-3-methyl-3-azabicyclo[3.1.0]hexan-6-yl)ethoxy)quinazolin-4,6-diamine	1363359-70-9	C₂₂H₂₃ClFN₅O	427.909
——	N-(4-(3-chloro-4-fluorophenyl))-7-(8-methyl-1-oxa-8-azaspiro[4.5]decan-3-yloxy)-6-nitroquinazolin-4-amine	1363359-63-0	C₂₃H₂₃ClFN₅O₄	487.918
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-4-(cyclopropylamino)but-2-enamide	——	C₂₂H₂₁ClFN₅O₂	441.892
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-(3-methyl-3-azabicyclo[3.2.1]octan-8-yl)ethoxy)quinazolin-4,6-diamine	——	C₂₄H₂₇ClFN₅O	455.963
——	N-(4-(3-chloro-4-fluorophenyl))-7-((6-methyl-6-azaspiro[2.5]octan-1-yl)methoxy)quinazolin-4,6-diamine	1363359-80-1	C₂₃H₂₅ClFN₅O	441.936
——	N-(4-(3-chloro-4-fluorophenyl))-7-(8-methyl-8-azabicyclo[3.2.1]octan-3-yloxy)quinazolin-4,6-diamine	1363359-62-9	C₂₂H₂₃ClFN₅O	427.909
——	N-(3-chloro-4-fluorophenyl)-6-amino-7-(3-D-tetrahydrafuran-3-yloxy)qunazolin-4-amine	1313875-08-9	C₁₈H₁₆ClFN₄O₂	375.794
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-4-(cyclopropyl(methyl)amino)but-2-enamide	——	C₂₃H₂₃ClFN₅O₂	455.919
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-ethoxyquinazolin-6-yl)-4-(cyclopropylamino)but-2-enamide	——	C₂₃H₂₃ClFN₅O₂	455.919
——	7-(7-oxabicyclo[2.2.1]heptan-2-yloxy)-N-(4-(3-chloro-4-fluorophenyl))quinazolin-4,6-diamine	1363359-58-3	C₂₀H₁₈ClFN₄O₂	400.84
达克替尼	Dacomitinib	1110813-31-4	C₂₄H₂₅ClFN₅O₂	469.946
——	7-(6-acrylamido-4-(3-chloro-4-fluorophenylamino)quinazolin-7-yloxy)-N-hydroxyheptanamide	——	C₂₄H₂₅ClFN₅O₄	501.945
——	8-(6-acrylamido-4-(3-chloro-4-fluoroanilino)quinazoline-7-yloxy)-N-hydroxyoctanamide	——	C₂₅H₂₇ClFN₅O₄	515.972
——	(E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-2-(4-cyanobenzylidene)hydrazine carboxamide	——	C₂₄H₁₇ClFN₇O₂	489.896
——	6-(6-acrylamido-4-(3-chloro-4-fluoroanilino)quinazoline-7-yloxy)-N-hydroxycaproamide	——	C₂₃H₂₃ClFN₅O₄	487.918
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-methoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide	1402086-40-1	C₂₃H₂₅ClFN₅O₃	473.935
——	(E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-2-(4-hydroxybenzylidene)hydrazine carboxamide	——	C₂₃H₁₈ClFN₆O₃	480.886
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-4-(dicyclopropylamino)but-2-enamide	——	C₂₅H₂₅ClFN₅O₂	481.957
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide	——	C₂₄H₂₇ClFN₅O₃	487.961
——	N-(4-(3-chloro-4-fluorophenyl))-7-((5-methyl-5-azaspiro[2.4]heptan-1-yl)methoxy)quinazolin-4,6-diamine	1363359-78-7	C₂₂H₂₃ClFN₅O	427.909
——	(E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-2-(4-methoxybenzylidene)hydrazine carboxamide	——	C₂₄H₂₀ClFN₆O₃	494.913
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(difluoromethoxy)quinazolin-6-yl)-4-(cyclopropylamino)but-2-enamide	——	C₂₂H₁₉ClF₃N₅O₂	477.873
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-isopropoxyethoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide	——	C₂₅H₂₉ClFN₅O₃	501.988
——	N-(4-(3-chloro-4-fluorophenyl))-7-(8-methyl-1-oxa-8-azaspiro[4.5]decan-2-ylmethoxy)quinazolin-4,6-diamine	1363359-68-5	C₂₄H₂₇ClFN₅O₂	471.962
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2,2,2-trifluoroethoxy)quinazolin-6-yl)-4-(cyclopropylamino)but-2-enamide	——	C₂₃H₂₀ClF₄N₅O₂	509.891
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4,4,4-trifluorobut-2-enamide	——	C₂₂H₁₉ClF₄N₄O₃	498.864
——	(E)-N-[4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl]-4-[2-azaspiro[ 3.4]octan-2-yl]-2-butenamide	1414884-63-1	C₂₆H₂₇ClFN₅O₂	495.984
——	N-(4-(3-chloro-4-fluorophenyl))-7-((8-methyl-1-oxa-8-azaspiro[4.5]decan-3-yl)methoxy)quinazolin-4,6-diamine	1363359-66-3	C₂₄H₂₇ClFN₅O₂	471.962
——	(E)-N-[4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl]-4-[2-azaspiro[ 3.5]nonan-2-yl]-2-butenamide	1414884-64-2	C₂₇H₂₉ClFN₅O₂	510.011
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(3-methoxypropoxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide	——	C₂₄H₂₇ClFN₅O₃	487.961
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-ethoxyethoxy)quinazolin-6-yl)-4-(diethylamino) but-2-enamide	——	C₂₆H₃₁ClFN₅O₃	516.015
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-ethoxyquinazolin-6-yl)-4-(dicyclopropylamino)but-2-enamide	——	C₂₆H₂₇ClFN₅O₂	495.984
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-methoxyethoxy)quinazolin-6-yl)-4-(cyclopropyl(methyl)amino)but-2-enamide	——	C₂₅H₂₇ClFN₅O₃	499.972
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-methoxyethoxy)quinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide	——	C₂₆H₂₉ClFN₅O₃	513.999
卡奈替尼	canertinib	267243-28-7	C₂₄H₂₅ClFN₅O₃	485.946
——	N-(4-(3-chloro-4-fluorophenyl))-7-(2-methyl-2,7-diazaspiro[4.5]decan-7-yl)quinazolin-4,6-diamine	1363359-60-7	C₂₃H₂₆ClFN₆	440.951
——	(R,E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}-3-[1-methylpyrrolidin-2-yl]propenamide	——	C₂₃H₂₃ClFN₅O₂	455.919
——	(S,E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazoline-6-yl}-3-[1-methylpyrrolidin-2-yl]propenamide	——	C₂₃H₂₃ClFN₅O₂	455.919
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-4-(thiomorpholine-1-oxide-4-yl)but-2-enamide	——	C₂₃H₂₃ClFN₅O₃S	503.985
——	N-(4-(3-chloro-4-fluorophenyl))-7-((7-methyl-7-azabicyclo[2.2.1]heptan-2-yl)methoxy)quinazolin-4,6-diamine	1363359-74-3	C₂₂H₂₃ClFN₅O	427.909
——	(S)-N-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)acrylamide	1402086-20-7	C₂₁H₁₈ClFN₄O₃	428.85
——	(S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-2-(4-nitrobenzylidene)hydrazine carboxamide	——	C₂₆H₂₁ClFN₇O₅	565.948
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(2-methoxyethoxy)quinazolin-6-yl)-4-(dicyclopropylamino)but-2-enamide	——	C₂₇H₂₉ClFN₅O₃	526.01
——	(E)-N-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-4-(3, 3-difluorocyclobutylamino)but-2-enamide	——	C₂₃H₂₁ClF₃N₅O₂	491.9

反应信息

作为反应物：

描述：

N-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺在 iron(III) chloride 、 potassium tert-butylate 、 N,N'-羰基二咪唑、 potassium hydroxide 作用下，以四氢呋喃、水、丙酮、叔丁醇为溶剂，反应 7.0h，生成阿法替尼

参考文献：

名称：

一种阿法替尼制备方法

摘要：

本发明揭示了一种新颖阿法替尼制备方法，包括如下步骤：N‑(3‑氯‑4‑氟苯基)‑7‑氟‑6‑硝基‑4‑喹唑啉胺还原得N‑(3‑氯‑4‑氟苯基)‑7‑氟‑6‑氨基‑4‑喹唑啉胺Ⅳ，再与二乙磷乙酸发生缩合反应得Ⅲ，再与二甲氨基乙醛缩二乙醇发生Wittig‑Horner‑Emmons反应得关键中间体Ⅱ,将化合物Ⅱ与(S)‑3‑羟基四氢呋喃进行取代反应得化合物Ⅰ。本发明方法收率高、纯度高。

公开号：

CN107488171B
作为产物：

描述：

N-(2-cyano-5-fluorophenyl)acetamide 在盐酸、硫酸、硝酸作用下，以甲苯为溶剂，反应 5.0h，生成 N-(3-氯-4-氟苯基)-7-氟-6-硝基-4-喹唑啉胺

参考文献：

名称：

发现作为不可逆的双重EGFR / HER2双重抑制剂的喹唑啉衍生物及其抗癌活性-第1部分。

摘要：

在许多乳腺癌，卵巢癌，结肠癌和前列腺癌中均观察到EGFR和HER2的过度表达。在FDA批准阿法替尼（Afatinib）克服突变相关问题之后，第二和第三代不可逆EGFR / HER2双激酶抑制剂开始流行。为了找到有效的候选药物，设计，合成和评估了一系列新型的喹唑啉衍生物，作为双EGFR / HER2酪氨酸激酶（TK）抑制剂。此处报道了选定的二十四种化合物，它们具有对EGFR / HER2酪氨酸激酶的显着抑制活性。几种化合物显示出纳摩尔IC50值。在NCI-H1975，HCC827，A431，MDA MB-453细胞系上进行了喹唑啉衍生物的体外研究。与标准药物afatinib相比，发现化合物1a，1d和1v更有效。

DOI：

10.1016/j.bmcl.2018.12.056

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文献信息

一种阿法替尼的制备方法

申请人：山东新时代药业有限公司

公开号：CN107488172B

公开（公告）日：2020-06-12

本发明属于医药技术领域，具体揭示了一种阿法替尼的制备方法，包括以中间体Ⅱ与(S)‑3‑羟基四氢呋喃发生取代反应得阿法替尼Ⅰ。该方法工艺简单、经济环保、终产品纯度高，适合工艺化放大的要求。
一种阿法替尼中间体及其合成方法

申请人：山东新时代药业有限公司

公开号：CN107488152B

公开（公告）日：2020-12-29

本发明揭示了一种新颖阿法替尼的中间体Ⅳ及其制备方法，包括如下步骤：N‑(3‑氯‑4‑氟苯基)‑7‑氟‑6‑硝基‑4‑喹唑啉胺还原得N‑(3‑氯‑4‑氟苯基)‑7‑氟‑6‑氨基‑4‑喹唑啉胺Ⅳ。本发明方法收率高、纯度高。
METHOD FOR PREPARING AFATINIB AND INTERMEDIATE THEREOF

申请人：Xu Xuenong

公开号：US20160083373A1

公开（公告）日：2016-03-24

Revealed in the present invention is a method for preparing Afatinib (I): using 2-nitrile-4-[4-(N,N-dimethylamino)-I-oxo-2-buten-I-yl]amino-5-[(S)-(tetrahydrofuran-3-yl)oxy]aniline (II) and 4-fluoro-3-chloroaniline (III) as starting materials, and respectively performing a condensation and cyclization reaction with N,N-dimethylformamide dimethyl acetal (IV) to prepare Afatinib (I), wherein the method significantly reduces the manufacturing steps of Afatinib and greatly lower the costs. In addition, also provided in the present invention is a method for preparing an intermediate of Afatinib, wherein the method has a stable process, uses readily available starting materials, has a low cost, and all the reactions are classic reactions, suitable for meeting amplification requirements in the industry.

本发明揭示了一种制备阿法替尼（I）的方法：使用2-腈基-4-[4-(N,N-二甲基氨基)-1-氧代-2-丁烯-1-基]氨基-5-[(S)-(四氢呋喃-3-基)氧基]苯胺（II）和4-氟-3-氯苯胺（III）作为起始原料，分别与N,N-二甲基甲酰胺二甲基缩醛（IV）进行缩合和环化反应制备阿法替尼（I），该方法显著减少了阿法替尼的制造步骤，大大降低了成本。此外，本发明还提供了一种制备阿法替尼中间体的方法，该方法具有稳定的工艺过程，使用易得的起始原料，成本低廉，并且所有反应均为经典反应，适合满足行业中的扩产需求。
一种阿法替尼中间体化合物

申请人：山东新时代药业有限公司

公开号：CN107488153B

公开（公告）日：2020-06-23

本发明揭示了一种新颖阿法替尼的中间体Ⅱ及其制备方法，包括如下步骤：N‑(3‑氯‑4‑氟苯基)‑7‑氟‑6‑硝基‑4‑喹唑啉胺还原得N‑(3‑氯‑4‑氟苯基)‑7‑氟‑6‑氨基‑4‑喹唑啉胺Ⅳ，再与二乙磷乙酸发生缩合反应得Ⅲ，再与二甲氨基乙醛缩二乙醇发生Wittig‑Horner‑Emmons反应得关键中间体Ⅱ。本发明方法收率高、纯度高。
[EN] AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'AMINOQUINAZOLINE, LEURS SELS ET LEURS PROCÉDÉS D'UTILISATION

申请人：SUNSHINE LAKE PHARMA CO LTD

公开号：WO2014177038A1

公开（公告）日：2014-11-06

Provided herein are aminoquinazoline compounds, salts and uses thereof. The compounds have Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Also provided herein are pharmaceutical compositions containing the compounds disclosed herein, and uses of the compounds or the compositions for preventing, managing, treating or lessening the severity of a proliferative disorder in a patient and for modulating the protein tyrosine kinase activity.

本文提供了氨基喹唑啉化合物、盐及其用途。这些化合物具有式(I)，或其立体异构体、几何异构体、互变异构体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药。本文还提供了含有上述化合物的药物组合物，以及利用这些化合物或组合物预防、管理、治疗或减轻患者体内增殖性疾病的严重程度，并调节蛋白酪氨酸激酶活性的用途。