22246-18-0

Basic information

• Product Name: 3,4-Dihydro-7-hydroxy-2(1H)-quinolinone
• Synonyms: 7-Hydroxy-3,4-dihydro-2(1H)-chinolinon;Intermediate of Aripiprazole;7-Hydroxy-3,4-dihydro-2(1H)-quinolinone;Aripiprazole Dihydroquinolinone Impurity (USP);Aripiprazole Impurity 13;7-Hydroxy-3,4-dihydro-2(1H)-quinolinone 97%;Aripiprazole Dihydroquinolinone Impurity;7-HYDROXY-2-OXO-3,4-DIHYDROQUINOLINE, 98% ARIPIPRZAOLE INTERMEDIATE
• CAS NO: 22246-18-0
• Molecular Formula: C₉H₉NO₂
• Molecular Weight: 163.17
• Product Categories: Quinoline derivatives;INTERMEDIATESOFARIPIPRAZOLE;Aromatics Compounds;Intermediates of Aripiprazole;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Heterocycles;Quinolines, Quinazolines and derivatives
• Mol File: 22246-18-0.mol
• Article Data: 24

Chemical Properties

• Melting Point: 233-237 °C
• Boiling Point: 403.7 °C at 760 mmHg
• Flash Point: 198 °C
• Appearance: Pale yellow powder
• Density: 1.282 g/cm³
• Vapor Pressure: 4.28E-07mmHg at 25°C
• Refractive Index: 1.604
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.60±0.20(Predicted)
• CAS DataBase Reference: 3,4-Dihydro-7-hydroxy-2(1H)-quinolinone(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-Dihydro-7-hydroxy-2(1H)-quinolinone(22246-18-0)
• EPA Substance Registry System: 3,4-Dihydro-7-hydroxy-2(1H)-quinolinone(22246-18-0)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-43
• Safety Statements: 36/37
• WGK Germany: 3
• Hazardous Substances Data: 22246-18-0(Hazardous Substances Data)

Usage

Description

3,4-Dihydro-7-hydroxy-2 (1H)-quinolinone is a useful organic and pharmaceutical intermediate. It can be used as the precursor of aripiprazole1, which is an antipsychotic medication. It is also an antitumor agent and hydroxyindole analog inhibitor tyrosinase melanoma.

Chemical Properties

Pale Yellow Powder

Uses

3,4-Dihydro-7-hydroxyquinoline-2(1H)-one (Aripiprazole EP Impurity A) is an antitumor agent. Hydroxyindole analog inhibitor tyrosinase melanoma. This compound is also used in the preparation of aripiprazole (A771000).

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

3-chloro-N-(3-hydroxyphenyl)propanamide (50297-40-0) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
With aluminum (III) chloride In N,N-dimethyl-formamide at 90 - 150℃; for 6h; Cooling with ice;	88%
Stage #1: 3-chloro-N-(3-hydroxyphenyl)propanamide With aluminum (III) chloride at 210℃; for 0.5h; Stage #2: With water at 20℃;	76%
With aluminum (III) chloride In N,N-dimethyl acetamide at 130 - 140℃;	68%

3-chloro-N-(3-methoxyphenyl)propionamide (21261-76-7) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
aluminum (III) chloride In N,N-dimethyl acetamide at 140 - 150℃; for 2.75h; Friedel Crafts Alkylation;	82%
With aluminium trichloride; N,N-dimethyl acetamide at 150 - 160℃; for 2h; Friedel-Crafts reaction;	61.5%
With aluminum (III) chloride In N,N-dimethyl acetamide at 0 - 150℃; for 2h;	54%

C9H7NO5 (1127347-52-7) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
With ammonium formate on silica gel; zinc In carbon dioxide at 50℃; under 90009 Torr; Autoclave; liquid CO2;	78%

4-benyzloxy-2-nitrobenzenediazonium tetrafluoroborate + acrylic acid methyl ester (292638-85-8) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
Stage #1: 4-benyzloxy-2-nitrobenzenediazonium tetrafluoroborate; acrylic acid methyl ester With palladium diacetate In 1,4-dioxane at 25℃; for 6h; Heck reduction-cyclisation-debenzylation reaction; Stage #2: With hydrogen; palladium diacetate; pyrographite In 1,4-dioxane at 50℃; for 24h; Heck reduction-cyclisation-debenzylation reaction;	66%

3-chloro-N-(3-methoxyphenyl)propionamide (21261-76-7) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 5-hydroxycarbostyril (30389-33-4)

Conditions	Yield
Stage #1: N-(3-methoxyphenyl)-3-chloropropionamide; aluminum (III) chloride at 155 - 165℃; for 4h; Stage #2: With methanol; sodium hydroxide In water at 20℃; for 1h; pH=7; Product distribution / selectivity; Heating / reflux;	A 62.3% B n/a
Stage #1: N-(3-methoxyphenyl)-3-chloropropionamide With N,N-dimethyl acetamide; aluminum (III) chloride In water at 95 - 165℃; for 5.5h; Stage #2: With methanol; sodium hydroxide In water at 20℃; for 1h; pH=7; Product distribution / selectivity; Heating / reflux;	A 61.3% B n/a
Stage #1: N-(3-methoxyphenyl)-3-chloropropionamide; aluminum (III) chloride In water at 95 - 165℃; for 5.5h; Stage #2: With methanol; sodium hydroxide In water at 20℃; for 1h; pH=7; Product distribution / selectivity; Heating / reflux;	A 61.3% B n/a

aluminum chloride powder + 3-chloro-N-(3-methoxyphenyl)propionamide (21261-76-7) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
In ice-H2O	55%

7-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline (22246-17-9) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
With hydrogen bromide

3-chloro-N-(3-hydroxyphenyl)propanamide (50297-40-0) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 5-hydroxy-3,4-dihydro-1H-quinolin-2-one

Conditions	Yield
With aluminium trichloride beim Schmelzen;

m-Anisidine (536-90-3) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent / NaHCO3 / CH2Cl2 / 4 h / 20 °C 2: 61.5 percent / N,N-dimethylacetamide; aluminium trichloride / 2 h / 150 - 160 °C View Scheme
Multi-step reaction with 2 steps 1: 95 percent / aq. K2CO3 / acetone / 1 h / 0 °C 2: 4 percent / AlCl3 / chlorobenzene / 6 h / 120 °C View Scheme
Multi-step reaction with 2 steps 1: sodium carbonate / toluene / 2 h / 40 - 65 °C 2: aluminum (III) chloride / N,N-dimethyl acetamide / 140 - 150 °C View Scheme
Multi-step reaction with 2 steps 1: pyridine / tetrahydrofuran / 0 - 20 °C 2: aluminum (III) chloride; N,N-dimethyl acetamide / 4 h / 140 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / toluene / 2 h / 50 °C 2: aluminum (III) chloride / N,N-dimethyl acetamide / 2 h / 0 - 150 °C View Scheme

methyl (E)-3-(4′-methoxy-2′-nitrophenyl)acrylate (103986-96-5) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Raney nickel; ethanol / Hydrogenation 2: aqueous hydrobromic acid View Scheme

2-chloropropionyl chloride (625-36-5) + m-Hydroxyaniline (591-27-5) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

4-hydroxy-2-nitrobenzenediazonium tetrafluoroborate + acrylic acid methyl ester (292638-85-8) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
Stage #1: 4-hydroxy-2-nitrobenzenediazonium tetrafluoroborate; acrylic acid methyl ester With sodium acetate; palladium diacetate In methanol at 20℃; for 12h; Mizoroki-Heck reaction; Inert atmosphere; Stage #2: With hydrogen; pyrographite In methanol at 20℃; under 750.075 Torr; for 24h; Stage #3: With hydrogenchloride In methanol; water	360 mg

N-(4-hydroxy-2-nitrophenyl)-acetamide (7403-75-0) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: boron trifluoride - methanol (1/1) / methanol / 5 h / Inert atmosphere; Reflux 1.2: 0.33 h / -15 - 0 °C 2.1: sodium acetate; palladium diacetate / methanol / 12 h / 20 °C 3.1: pyrographite; hydrogen / methanol / 24 h / 750.08 Torr View Scheme

C10H9NO5 → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
With hydrogen; pyrographite In methanol under 750.075 Torr; for 24h;	360 mg

m-Hydroxyaniline (591-27-5) → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / acetonitrile / 0 °C 2: aluminum (III) chloride / dichloromethane View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / 2 h / 25 °C / pH 9 2: boron trifluoride diethyl etherate / toluene / 2 h / 60 °C View Scheme
Multi-step reaction with 2 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 View Scheme

C9H11NO3 → 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0)

Conditions	Yield
With boron trifluoride diethyl etherate In toluene at 60℃; for 2h; Temperature;

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + tert-butyldimethylsilyl chloride (18162-48-6) → 7-(tert-butyl-dimethylsilanyloxy)-3,4-dihydro-1H-quinolin-2-one (1427053-51-7)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0℃;	99.4%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-hydroxy-1,2,3,4-tetrahydroquinoline (58196-33-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran Inert atmosphere; Cooling with ice; Reflux;	98%
With sodium tetrahydroborate In tetrahydrofuran at 0℃; Reflux;	98%
With lithium aluminium tetrahydride In tetrahydrofuran Cooling with ice; Reflux;	95%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 1-bromomethyl-3-chlorobenzene (766-80-3) → 7-((3-chlorobenzyl)oxy)-3,4-dihydroquinolin-2(1H)-one (1458219-01-6)

Conditions	Yield
With potassium carbonate In acetonitrile at 60℃; for 18h;	97%
With potassium carbonate In acetonitrile for 8h; Reflux;	68%
With potassium hydroxide In ethanol for 5h; Reflux;	32%

4-chlorobutyl bromide (6940-78-9) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one (120004-79-7)

Conditions	Yield
With lithium hydroxide In water; N,N-dimethyl-formamide at 40 - 50℃; for 3h; Reagent/catalyst; Solvent; Sealed tube; Large scale;	95%
With potassium carbonate; polyethylene glycol-400 In water; acetone at 20℃; for 15.1667 - 16.1667h;	94%
With potassium carbonate In N,N-dimethyl-formamide at 20 - 30℃; for 24h; Solvent; Temperature; Large scale;	93.2%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 2-Bromo-2'-acetonaphthone (613-54-7) → 7-[2-(naphthalen-2-yl)-2-oxoethoxy]-3,4-dihydroquinolin-2(1H)-one (1303566-73-5)

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 2-Bromo-2'-acetonaphthone In N,N-dimethyl-formamide at 20℃; for 24h;	95%
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 2-Bromo-2'-acetonaphthone In N,N-dimethyl-formamide at 20℃; for 24h;	88%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 4-chlorobutanal dimethyl acetal (29882-07-3) → 7-(4,4-dimethoxybutoxy)-3,4-dihydro-1H-quinolin-2-one (1359159-57-1)

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In dimethyl sulfoxide at 115℃; for 4h;	95%

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%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 4-methoxy-benzoyl chloride (100-07-2) → 7-(4-methoxybenzoyloxy)-3,4-dihydro-1H-quinolin-2-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h;	93.3%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 1,4-dichlorobutane-d8 → C13H8(2)H8ClNO2

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 3h; Inert atmosphere;	92%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + C14H19Cl3N2*ClH → aripiprazole (129722-12-9)

Conditions	Yield
With potassium carbonate In water at 99℃; for 5h; Reagent/catalyst; Temperature;	91.4%

1,4-dibromo-butane (110-52-1) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone (129722-34-5)

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In water; acetone at 20℃; for 1h; Stage #2: 1,4-dibromo-butane In water; acetone at 20℃; for 16h;	91%
With potassium iodide; sodium hydroxide In acetonitrile at 30℃; for 16h;	85%
With sodium hydroxide In ethanol for 2.5h; Heating;	83%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 1,4-dichlorobutane (110-56-5) → 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one (120004-79-7)

Conditions	Yield
With potassium carbonate In propan-1-ol for 8 - 10h; Product distribution / selectivity; Heating / reflux;	91%
With potassium carbonate; sodium sulfate; Aliquat 336 In toluene for 14h; Product distribution / selectivity; Heating / reflux;	75%
With potassium carbonate In ISOPROPYLAMIDE at 90 - 95℃; for 15 - 16h;	75%
With potassium carbonate In acetonitrile for 22h; Product distribution / selectivity; Heating / reflux;	74%
With potassium carbonate In propan-1-ol; isopropyl alcohol for 19h; Product distribution / selectivity; Heating / reflux;	66%

1 ,6-dibromohexane (629-03-8) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-((6-bromohexyl)oxy)-3,4-dihydroquinolin-2(1H)-one (1303529-03-4)

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In water; acetone at 20℃; for 1h; Stage #2: 1 ,6-dibromohexane In water; acetone at 20℃; for 16h;	91%
With potassium carbonate In acetonitrile at 60 - 65℃; Inert atmosphere;	56.8%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone (129722-34-5) → 7-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-oxy)butoxy)-3,4-dihydroquinoline-2(1H)-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃;	90.9%
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With sodium hydroxide In methanol for 2h; Heating; Stage #2: 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone In N,N-dimethyl-formamide at 20℃; Further stages.;	16.8 g
With potassium hydroxide In ethanol Reflux;

1,5-dibromo-pentane (111-24-0) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-((5-bromopentyl)oxy)-3,4-dihydroquinolin-2(1H)-one (63309-41-1)

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In water; acetone at 20℃; for 1h; Stage #2: 1,5-dibromo-pentane In water; acetone at 20℃; for 16h;	90%
With potassium carbonate In acetonitrile at 60 - 65℃; Inert atmosphere;	60.2%
With potassium hydroxide In isopropyl alcohol for 4h; Heating;	53%
With potassium carbonate In acetonitrile at 50℃; for 20h;

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + methyl iodide (74-88-4) → 7-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline (22246-17-9)

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In isopropyl alcohol at 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In isopropyl alcohol for 60h; Reflux;	90%
In N,N-dimethyl-formamide at 20℃;	82%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 18h;	63%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 1,3-dibromo-propane (109-64-8) → 7-(3-bromopropoxy)-3,4-dihydroquinolin-2(1H)-one (82657-32-7)

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In water; acetone at 20℃; for 1h; Stage #2: 1,3-dibromo-propane In water; acetone at 20℃; for 16h;	90%
With potassium carbonate In ethanol Reflux;	88%
With potassium carbonate In acetonitrile at 60 - 65℃; Inert atmosphere;	65.3%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + t-butyl 4-(2-nitrophenylsulfonyloxy)piperidine-1-carboxylate (1092366-87-4) → tert-butyl 4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]piperidine-1-carboxylate (583031-07-6)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 7h; Williamson Synthesis;	87%
With triethylamine In dichloromethane

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 6-bromo-7-hydroxy-3,4-dihydro-1H-quinolin-2-one (1194459-28-3)

Conditions	Yield
With N-Bromosuccinimide In N,N-dimethyl-formamide at 0℃; for 9h;	87%
With N-Bromosuccinimide	58%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 0 - 20℃;	0.82 g

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + trifluoromethylsulfonic anhydride (358-23-6) → 2-oxo-1,2,3,4-tetrahydroquinolin-7-yl trifluoromethanesulfonate (882023-50-9)

Conditions	Yield
With pyridine In dichloromethane at 10 - 30℃; for 3h;	85%
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With pyridine In chloroform at 20℃; for 0.166667h; Stage #2: trifluoromethylsulfonic anhydride In chloroform at 20℃; for 1.5h; Cooling with ice;	67%
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With pyridine In chloroform at 0 - 40℃; for 0.166667h; Stage #2: trifluoromethylsulfonic anhydride In chloroform at 10 - 15℃; for 1.58333h;
With pyridine In chloroform at 0 - 23℃; for 18h; Inert atmosphere; Schlenk technique;

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + α-bromoacetophenone (70-11-1) → 3,4-dihydro-7-(2-oxo-2-phenylethoxy)quinolin-2(1H)-one

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; deprotonation; Stage #2: α-bromoacetophenone In N,N-dimethyl-formamide at 20℃; for 24h; Alkylation;	84%
With potassium carbonate

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + benzyl bromide (100-39-0) → 7-(benzyloxy)-3,4-dihydro-2(1H)-quinolinone (92962-89-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 16h;	84%
With potassium carbonate In acetonitrile Heating;	79%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;	67%
With potassium hydroxide In ethanol for 5h; Reflux;	57%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + (4-bromobutoxy)-tert-butyldimethylsilane (89043-32-3) → 7-(4-((tert-butyldimethylsilyl)oxy)butoxy)-3,4-dihydroquinolin-2(1H)-one

Conditions	Yield
With potassium carbonate In ethanol Reflux;	84%
With potassium carbonate; potassium iodide Reflux;	84%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + 2-Bromo-4'-phenylacetophenone (135-73-9) → 7-[2-(1,1'-biphenyl-4-yl)-2-oxoethoxy]-3,4-dihydroquinolin-2(1H)-one

Conditions	Yield
Stage #1: 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; deprotonation; Stage #2: 2-Bromo-4'-phenylacetophenone In N,N-dimethyl-formamide at 20℃; for 24h; Alkylation;	80%
With potassium carbonate

4-chlorobutyl bromide (6940-78-9) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-oxy)butoxy)-3,4-dihydroquinoline-2(1H)-one + 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one (120004-79-7)

Conditions	Yield
With sodium hydroxide In ISOPROPYLAMIDE at 36 - 40℃; for 4h; Product distribution / selectivity;	A 0.3% B 80%

7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) + N,N-diethylcarbamyl chloride (88-10-8) → 2-oxo-1,2,3,4-tetrahydroquinolin-7-yl diethylcarbamate

Conditions	Yield
With pyridine for 12h; Reflux;	80%

2-(morpholin-4-yl)ethanol (622-40-2) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-(2-morpholinoethoxy)-3,4-dihydroquinolin-2(1H)-one (1609210-11-8)

Conditions	Yield
With cyanomethylenetributyl-phosphorane In toluene at 100℃; for 16h; Mitsunobu Displacement;	80%

2-(4-methylpiperazinyl)ethanol (5464-12-0) + 7-hydroxy-3,4-dihydro-2-(1H)-quinolinone (22246-18-0) → 7-[2-(4-methylpiperazin-1-yl)ethoxy]-3,4-dihydroquinolin-2(1H)-one

Conditions	Yield
With cyanomethylenetributyl-phosphorane In toluene at 100℃; for 16h; Mitsunobu Displacement;	80%

Upstream product

• 50297-40-0 3-chloro-N-(3-hydroxyphenyl)propanamide 
• 1127347-52-7 C₉H₇NO₅ 
• 7403-75-0 N-(4-hydroxy-2-nitrophenyl)-acetamide 
• 591-27-5 m-Hydroxyaniline 
• 292638-85-8 acrylic acid methyl ester 
• 625-36-5 2-chloropropionyl chloride 
• 21261-76-7 N-(3-methoxyphenyl)-3-chloropropionamide 
• 103986-96-5 methyl (E)-3-(4′-methoxy-2′-nitrophenyl)acrylate 
• 536-90-3 m-Anisidine 
• 22246-17-9 7-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline 

Downstream Products

• 129722-34-5 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone 
• 120004-79-7 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one 
• 129722-12-9 aripiprazole 
• 73963-78-7 7-[3-(1-Cyclohexyltetrazol-5-yl)propoxy]-3,4-dihydrocarbostyril 
• 857272-53-8 7-(hydroxymethyl)-3,4-dihydroquinolin-2(1H)-one 
• 917836-04-5 2-oxo-1,2,3,4-tetrahydroquinoline-7-carbaldehyde 
• 22246-17-9 7-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline 

Relevant articles and documents

An innovative approach for the synthesis of 7-hydroxyquinolin-2(1H)-one: A key intermediate of brexpiprazole

2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ) mediated oxidation of 7-hydroxy-1,2,3,4-tetrahydro-2-quinolinone has been prepared from 3-hydroxy aniline to obtain 7-hydroxyquinolin-2(1H)-one in aqueous media. Stoichiometric quantities of DDQ and THF provides a high out put of 7-hydroxyquinolin-2(1H)-one and reduces the consumption of organic solvents and discourages by-products. Overall advantage with this approach was reduce the time cycle and cost of the brexpiprazole intermediate.

Design, synthesis, molecular docking, and in vitro antidiabetic activity of novel PPARγ agonist

Abstract: The present work describes the design, synthesis, molecular docking, biological evaluation, and assessment of structure–activity relationship of new derivatives based upon the molecular skeleton of the drug pioglitazone, a compound which is currently used for the management of type 2 diabetes mellitus. Pioglitazone has several side effects such as weight gain, edema, congestive heart failure, and bladder cancer. Therefore, there is a strong demand for identification of new lead candidates in the treatment of type 2 diabetes mellitus. A series of 24 compounds were prepared and evaluated for their peroxisome proliferator-activated receptor-γ (PPARγ) binding affinity assay and the IC50 values were determined. Among these compounds, six compounds exhibited promising IC50 values as compared to standard drugs pioglitazone and rosiglitazone. Furthermore, in order to confirm the target of these molecules, molecular docking study was carried out with peroxisome proliferator-activated receptor-γ (PPARγ) protein. Molecular modeling studies suggested that these compounds appropriately interact in the active sites of receptor. Graphical abstract: [Figure not available: see fulltext.].

Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins

The bromodomain and plant homeodomain finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here, we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRPF2 over BRPF3, whereas binding to BRD9 was weaker. Compound 16 has excellent selectivity over nonclass IV BRD proteins. Target engagement of BRPF1B and BRPF2 with 16 was demonstrated in nanoBRET and FRAP assays. The binding of 16 to BRPF1B was rationalized through an X-ray cocrystal structure determination, which showed a flipped binding orientation when compared to previous structures. We report studies that show 16 has functional activity in cellular assays by modulation of the phenotype at low micromolar concentrations in both cancer and inflammatory models. Pharmacokinetic data for 16 was generated in mouse with single dose administration showing favorable oral bioavailability.