70500-72-0

Basic information

• Product Name: 7-Hydroxyquinolinone
• Synonyms: 2,7-DIHYDROXYQUINOLINE;7-HYDROXY-2-QUINOLINONE;7-HYDROXY-1H-QUINOLIN-2-ONE;7-hydroxy-2-(1h)-quinolinone;7-HYDROXYQUINOLINE-2(1H)-ONE;7-hydroxyquinolinone;7-HYDROXYQUINOLINE-(1H)-2-ONE;3,4-Dihydro-7-hydroxyquinoline-2(1H)-one
• CAS NO: 70500-72-0
• Molecular Formula: C₉H₇NO₂
• Molecular Weight: 161.16
• EINECS: 1308068-626-2
• Product Categories: Aromatics Compounds;Quinoline;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycles
• Mol File: 70500-72-0.mol
• Article Data: 23

Chemical Properties

• Melting Point: 187-192°C
• Boiling Point: 403.7oC at 760 mmHg
• Flash Point: 198°C
• Appearance: /
• Density: 1.282g/cm3
• Vapor Pressure: 4.28E-07mmHg at 25°C
• Refractive Index: 1.604
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly, Sonicated)
• PKA: 9.32±0.20(Predicted)
• CAS DataBase Reference: 7-Hydroxyquinolinone(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Hydroxyquinolinone(70500-72-0)
• EPA Substance Registry System: 7-Hydroxyquinolinone(70500-72-0)

Safety Data

• Hazardous Substances Data: 70500-72-0(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Different sources of media describe the Uses of 70500-72-0 differently. You can refer to the following data:
1. 7-Hydroxyquinolone is a substituted carbostyril derivative used as a pharmaceutical intermediate. It is an impurity of aripiprazole quinolinone.
2. A substituted carbostyril derivative as pharmaceutical intermediate. Aripiprazole Quinolinone Impurity

InChI:InChI=1/C9H9NO2/c11-7-3-1-6-2-4-9(12)10-8(6)5-7/h1,3,5,11H,2,4H2,(H,10,12)

Synthetic route

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
With palladium 10% on activated carbon; water; oxygen; acetic acid at 110 - 116℃; for 18h; Reagent/catalyst; Temperature;	94.2%
With palladium 10% on activated carbon In decalin at 180℃; for 8h;	90.9%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran at 66℃; for 4h; Catalytic behavior; Concentration; Solvent; Temperature;	89%

2-oxo-1,2-dihydroquinolin-7-yl-acetate (220364-99-8) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
With sodium hydroxide In water for 1.5h;	90%

C18H20BNO6 → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Stage #1: C18H20BNO6 With aluminum (III) chloride; tris(pentafluorophenyl)borate In 5,5-dimethyl-1,3-cyclohexadiene at 0 - 70℃; for 2h; Stage #2: With dihydrogen peroxide; acetic acid In 5,5-dimethyl-1,3-cyclohexadiene at 0 - 20℃; for 2h;	82.2%

C17H18BNO5 → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Stage #1: C17H18BNO5 With aluminum (III) chloride; tris(pentafluorophenyl)borate In toluene at 0 - 90℃; for 2h; Stage #2: With dihydrogen peroxide; acetic acid In toluene at 0 - 20℃; for 2h;	81.3%

(2E)-N-(3-methoxyphenyl)-3-phenylacrylamide (127033-74-3) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
With aluminium trichloride In chlorobenzene at 120℃; for 2h;	70%
With aluminium trichloride In chlorobenzene	70%
With aluminum (III) chloride In chlorobenzene at 0℃; for 8h; Reflux;	67%

7-hydroxy-2H-chromen-2-one (93-35-6) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
With acetic acid In acetic acid for 3h; Substitution; Heating;	55%

N-(3-methoxyphenyl)cinnamamide (15116-41-3) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
With aluminum (III) chloride In chlorobenzene at 0 - 120℃;	53%
With aluminum (III) chloride at 120 - 180℃; for 2.08333h;	43%
With aluminum (III) chloride at 120 - 180℃; for 2h;

m-Anisidine (536-90-3) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent 2: 70 percent / AlCl3 / chlorobenzene View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / water; acetone / 20 °C / Cooling with ice 2: aluminum (III) chloride / chlorobenzene / 0 - 120 °C View Scheme
Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 1 h / 5 - 20 °C 2: aluminum (III) chloride / 2.08 h / 120 - 180 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone; water / 0.5 h 2: aluminum (III) chloride / chlorobenzene / 120 °C / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone; water / 0.5 h / 0 °C 2: aluminum (III) chloride / chlorobenzene / Reflux View Scheme

7-hydroxyquinoline 1-oxide (93499-67-3) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 24 percent / 2 h / Heating 2: 90 percent / 1.0 N NaOH / H2O / 1.5 h View Scheme

m-Anisidine (536-90-3) + glycocoll-alkyl ester hydrochloride → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / aq. K2CO3 / acetone / 0.5 h / 0 °C 2: 70 percent / AlCl3 / chlorobenzene / 2 h / 120 °C View Scheme

m-Hydroxyaniline (591-27-5) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
With pyridine; AlCl3 In dichloromethane; ethyl acetate
Multi-step reaction with 3 steps 1.1: sodium hydrogencarbonate / dichloromethane / 0.5 h / 20 °C / Inert atmosphere 1.2: 2 h / 20 °C / Inert atmosphere 2.1: aluminum (III) chloride / N,N-dimethyl acetamide / 4 h / 70 - 140 °C 3.1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / tetrahydrofuran / 2 h / 20 - 50 °C / Inert atmosphere 3.2: 1 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / ethyl acetate / 20 - 30 °C 2: aluminum (III) chloride / N,N-dimethyl acetamide / 130 - 140 °C 3: palladium 10% on activated carbon; water; acetic acid; oxygen / 18 h / 110 - 116 °C View Scheme

3-chloro-N-(3-hydroxyphenyl)propanamide (50297-40-0) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / N,N-dimethyl acetamide / 4 h / 70 - 140 °C 2.1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / tetrahydrofuran / 2 h / 20 - 50 °C / Inert atmosphere 2.2: 1 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: aluminum (III) chloride / N,N-dimethyl acetamide / 130 - 140 °C 2: palladium 10% on activated carbon; water; acetic acid; oxygen / 18 h / 110 - 116 °C View Scheme

3,4-dimethoxy-trans-cinnamic acid (14737-89-4) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene / 4 h / 70 °C 2.1: triethylamine / tetrahydrofuran / 2 h / -5 - 20 °C 3.1: tris(pentafluorophenyl)borate; aluminum (III) chloride / toluene / 2 h / 0 - 90 °C 3.2: 2 h / 0 - 20 °C View Scheme

(E)-3,4-dimethoxycinnamic chloride (39856-08-1, 141236-46-6) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 2 h / -5 - 20 °C 2.1: tris(pentafluorophenyl)borate; aluminum (III) chloride / toluene / 2 h / 0 - 90 °C 2.2: 2 h / 0 - 20 °C View Scheme

(E)-3,4,5-trimethoxy-cinnamic acid (20329-98-0, 20329-99-1, 90-50-6) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene / 4 h / 70 °C 2.1: pyridine / tetrahydrofuran / 2 h / -5 - 20 °C 3.1: tris(pentafluorophenyl)borate; aluminum (III) chloride / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 0 - 70 °C 3.2: 2 h / 0 - 20 °C View Scheme

(E)-3-(3,4,5-trimethoxyphenyl)acryloyl chloride (10263-19-1, 89652-61-9) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: pyridine / tetrahydrofuran / 2 h / -5 - 20 °C 2.1: tris(pentafluorophenyl)borate; aluminum (III) chloride / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 0 - 70 °C 2.2: 2 h / 0 - 20 °C View Scheme

m-Anisidine (536-90-3) + Cinnamoyl chloride (102-92-1) → 7-hydroxy-1H-quinolin-2-one (70500-72-0)

Conditions	Yield
Stage #1: m-Anisidine; Cinnamoyl chloride In dichloromethane for 4h; Reflux; Stage #2: With aluminum (III) chloride In chlorobenzene for 8h; Reflux;

7-hydroxy-1H-quinolin-2-one (70500-72-0) → 2-chloroquinoline-7-ol (375358-19-3)

Conditions	Yield
With trichlorophosphate In N,N-dimethyl-formamide at 70 - 75℃; Reagent/catalyst;	94%
With thionyl chloride In N,N-dimethyl-formamide at 0 - 70℃; for 1h;	80.9%

4-chlorobutyl bromide (6940-78-9) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4-chlorobutoxy)quinoline-2(1H)-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 40 - 50℃; for 5h;	93.7%
With triethylamine In ethanol at 60 - 80℃; for 2h; Concentration; Solvent; Temperature; Reagent/catalyst;	92.2%
With sodium hydroxide In ethanol for 5h; Reflux;	88%

acetic anhydride (108-24-7) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 2-oxo-1,2-dihydroquinolin-7-yl-acetate (220364-99-8)

Conditions	Yield
With indium(III) triflate at 0 - 30℃; for 1h;	90%

7-hydroxy-1H-quinolin-2-one (70500-72-0) + tert-butyl 4-bromobutylcarbamate (164365-88-2) → tert-butyl (4-((2-oxo-1,2-dihydroquinolin-7-yl)oxy)butyl)carbamate

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 45 - 55℃;	87.4%

1,4-dibromo-butane (110-52-1) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7–(4-bromobutoxy)quinolin-2(1H)-one (203395-59-9)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 3h; Reflux;	86.5%
With potassium carbonate In water; N,N-dimethyl-formamide at 30 - 40℃; for 4h;	82%
With potassium carbonate In acetone for 4h; Reflux;	78%

7-hydroxy-1H-quinolin-2-one (70500-72-0) + Diphenylphosphine oxide (4559-70-0) → 3-(diphenylphosphoryl)-7-hydroxyquinolin-2(1H)-one

Conditions	Yield
With eosin; dibenzoyl peroxide In water; dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; Irradiation; regioselective reaction;	86%

3,4-difluoronitrobenzene (369-34-6) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(2-fluoro-4-nitrophenoxy)quinolin-2(1H)-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	86%

1-bromo-4-aminobutane (33977-38-7) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4-aminobutoxy)quinolin-2(1H)-one

Conditions	Yield
Stage #1: 4-bromo-1-aminobutane With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 7-hydroxy-1H-quinolin-2-one With sodium iodide In N,N-dimethyl-formamide at 100℃; for 0.666667h; Temperature;	84.3%

tert-butyl 4-(4-chlorobutyl)piperazine-1-carboxylate + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → tert-butyl 4-(4-((2-oxo-1,2-dihydroquinolin-7-yl)oxy)butyl)piperazine-1-carboxylate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 80 - 90℃;	84.1%

7-(4-chlorobutoxy)quinoline-2(1H)-one + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4-(2-oxo-1,2-dihydroquinolin-7-oxy)butoxy)quinolin-2(1H)-one

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 80 - 90℃; for 20h;	83%

C16H21N2S(1+)*Br(1-) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → Brexpiprazole (913611-97-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 130 - 135℃; Reagent/catalyst; Temperature;	82%

4-Bromo-1-butanol (33036-62-3) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4-hydroxybutoxy)quinoline-2-(1H)-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 24h; Reflux;	81%
With potassium carbonate In water; N,N-dimethyl-formamide at 40 - 50℃;	81.4%

4-chlorobutanal dimethyl acetal (29882-07-3) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4,4-dimethoxybutoxy)quinolin-2(1H)-one

Conditions	Yield
Stage #1: 7-hydroxy-1H-quinolin-2-one With potassium carbonate In N,N-dimethyl-formamide at 25 - 35℃; for 0.5h; Stage #2: 4-chlorobutanal dimethyl acetal In N,N-dimethyl-formamide at 70 - 75℃; for 10h;	80%
With tetrabutylammomium bromide; potassium carbonate In dimethyl sulfoxide at 20 - 70℃; for 20h;

4-Chloro-1-butanol (928-51-8) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4-hydroxybutoxy)quinoline-2-(1H)-one

Conditions	Yield
Stage #1: 7-hydroxy-1H-quinolin-2-one With potassium carbonate In N,N-dimethyl-formamide at 25 - 35℃; for 0.5h; Stage #2: 4-Chloro-1-butanol In N,N-dimethyl-formamide at 70 - 75℃;	80%

7-hydroxy-1H-quinolin-2-one (70500-72-0) + 1,3-dibromo-propane (109-64-8) → 7–(3-bromopropoxy)quinolin-2(1H)-one (1076199-59-1)

Conditions	Yield
With potassium carbonate In acetone for 4h; Reflux;	79%
With potassium carbonate In ethanol Reflux;	55%
With potassium carbonate In acetonitrile at 50℃; for 20h;

7-hydroxy-1H-quinolin-2-one (70500-72-0) → 2-bromoquinolin-7-ol

Conditions	Yield
With phosphorus tribromide In N,N-dimethyl-formamide at 70 - 75℃;	79%

Methyl 4-bromobutyrate (4897-84-1) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 4-(2-Oxo-1,2-dihydro-quinolin-7-yloxy)-butyric acid methyl ester (87364-43-0)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In isopropyl alcohol for 4h; Heating;	78%

4-chloro-1,1-diethoxybutane (6139-83-9) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(4,4-diethoxybutoxy)quinolin-2(1H)-one

Conditions	Yield
With tetrabutylammomium bromide; sodium carbonate In dimethyl sulfoxide at 100 - 110℃; for 3h; Reagent/catalyst; Solvent; Temperature; Large scale;	78%

2,4-dichlorothieno[3,2-d]pyrimidine (16234-14-3) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-(2-chlorothieno[3,2-d]pyrimidin-4-yloxy)quinolin-2(1H)-one

Conditions	Yield
With potassium carbonate In water; acetonitrile at 70℃;	78%
With potassium carbonate In water; acetonitrile Reflux;	78%

C13H25N2O2(1+)*HO(1-) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → tert-butyl 4-(4-((2-oxo-1,2-dihydroquinolin-7-yl)oxy)butyl)piperazine-1-carboxylate

Conditions	Yield
With N,N-dimethyl acetamide; potassium carbonate; 4-methyl-2-pentanone at 116 - 118℃; for 20h; Reagent/catalyst;	77.9%

7-hydroxy-1H-quinolin-2-one (70500-72-0) + ethylene dibromide (106-93-4) → 7–(2-bromoethoxy)quinolin-2(1H)-one

Conditions	Yield
With potassium carbonate In acetone for 4h; Reflux;	77%
With potassium hydroxide In methanol at 65℃; for 4h; Inert atmosphere;	16.2%

1,5-dibromo-pentane (111-24-0) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-((5-bromopentyl)oxy)quinolin-2(1H)-one

Conditions	Yield
With potassium carbonate In acetone for 4h; Reflux;	76%
With potassium carbonate In acetonitrile at 50℃; for 20h;

7-hydroxy-1H-quinolin-2-one (70500-72-0) + 2-bromo-4'-fluoroacetophenone (403-29-2) → 7-<2-(4-fluorophenyl)-2-oxoethoxy>quinolin-2(1H)-one (220365-01-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 24.5h; Ambient temperature;	75%

1-ethyl-2-methylquinolinium iodide (606-55-3) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 1-ethyl-2-(7-hydroxy-1H-quinolin-2-ylidenemethyl)-quinolinium; iodide

Conditions	Yield
With piperidine In ethanol Condensation; Heating;	75%

7-hydroxy-1H-quinolin-2-one (70500-72-0) + allyl bromide (106-95-6) → 7-(prop-2-en-1-yloxy)-1,2-dihydroquinolin-2-one (177419-02-2)

Conditions	Yield
With potassium carbonate In acetone at 60℃; for 16h;	74%
With potassium carbonate In acetone at 60℃; for 16h;	74%

1 ,6-dibromohexane (629-03-8) + 7-hydroxy-1H-quinolin-2-one (70500-72-0) → 7-((6-bromohexyl)oxy)quinolin-2(1H)-one

Conditions	Yield
With potassium carbonate In acetone for 4h; Reflux;	74%

Upstream product

• 58336-33-7 7-amino-quinolin-2-ol 
• 93-35-6 7-hydroxy-2H-chromen-2-one 
• 580-20-1 quinolin-7-ol 
• 536-90-3 m-Anisidine 
• 102-92-1 Cinnamoyl chloride 
• 10263-19-1 (E)-3-(3,4,5-trimethoxyphenyl)acryloyl chloride 
• 20329-98-0 (E)-3,4,5-trimethoxy-cinnamic acid 
• 39856-08-1 (E)-3,4-dimethoxycinnamic chloride 
• 14737-89-4 3,4-dimethoxy-trans-cinnamic acid 
• 50297-40-0 3-chloro-N-(3-hydroxyphenyl)propanamide 
• 22246-18-0 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone 
• 15116-41-3 N-(3-methoxyphenyl)cinnamamide 
• 591-27-5 m-Hydroxyaniline 
• 93499-67-3 7-hydroxyquinoline 1-oxide 

Downstream Products

• 220365-00-4 7-(2-oxo-2-phenylethoxy)quinolin-2(1H)-one 
• 220365-02-6 7-<2-(4-chlorophenyl)-2-oxoethoxy>quinolin-2(1H)-one 
• 220365-03-7 7-<2-(4-bromophenyl)-2-oxoethoxy>quinolin-2(1H)-one 
• 220365-01-5 7-<2-(4-fluorophenyl)-2-oxoethoxy>quinolin-2(1H)-one 
• 220365-04-8 7-<2-(4-methoxyphenyl)-2-oxoethoxy>quinolin-2(1H)-one 
• 473907-59-4 7-[2-oxo-2-(1,1'-biphenyl-4-yl)ethoxy]quinolin-2(1H)-one 
• 1354030-20-8 7-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1354030-31-1 7-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1354030-37-7 7-(4-(4-(2-ethoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1354030-38-8 7-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)quinolin-2(1H)-one 
• 1354030-42-4 7-(4-(4-(2-isopropoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1076199-59-1 7–(3-bromopropoxy)quinolin-2(1H)-one 
• 49609-15-6 2-chloro-7-methoxyquinoline 
• 386273-52-5 7-(benzyloxy)quinolin-2(1H)-one 

Relevant articles and documents

Preparation method of brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone

The invention belongs to the field of chemical engineering, and particularly relates to a preparation method of a brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone. According to the novel method for preparing the 7-hydroxy-1H-quinoline-2-ketone, DDQ is replaced with palladium on carbon, the obtained product is high in yield, few in impurity and easy to operate, the catalyst can be recycled, a target compound is synthesized through direct catalytic dehydrogenation, and the method has green atom economy and is suitable for industrial production.

Discovery of new thieno[3,2-d]pyrimidine derivatives targeting EGFRL858R/T790M NSCLCs by the conformation constrained strategy

Studies on the third-generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFRL858R/T790M mutant remain hotspots, specifically for non-small cell lung cancer (NSCLC). In the current study, a new series of EGFR-TKIs with thieno[3,2-d]pyrimidine derivatives(6a-6r) bearing quinolin-2(1H)-ones were designed and synthesized, through conformational constrained strategy from the third generation of EGFR-TKI olmutinib. In vitro structure-activity relationship (SAR) studies indicated that compounds 6a, 6l, 6m, 6n and 6o exhibited good selective inhibition to EGFRL858R/T790M (IC50 ≤ 250 nM) over wild type EGFR (IC50 > 10000 nM). The observed selectivity of compounds 6l and 6o was also proved by the computational molecular docking and the cellular thermal shift assay. These compounds had good growth inhibitory effect on the four tested cancer cell lines. Specifically, 6o could significantly inhibit the colony formation, wound healing and the expression of p-EGFR and its downstream p-ERK in EGFRL858R/T790M H1975 lung cancer cells. Our findings suggest that the thieno[3,2-d]pyrimidine compounds, especially 6l and 6o, can selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs.

A 7 - hydroxy -2 - quinolinone of preparation method

The invention discloses a formula I compound represented by the preparation method, the method comprises the following steps: in a solvent, in the arrowhead class under the action of the catalyst, on the compound II are shown in the following of the dehydrogenation reaction to obtain the compound I can be. Preparation method of this invention has the following advantages: the raw materials used are cheap, product yield and high purity, the purity of 98% or more, the color white and non-heterogeneous, after treatment is simple, catalyst and solvent can be recycled, wastes very little, for environmental protection, it is suitable for industrial production.