286371-49-1

Basic information

• Product Name: 7-Benzyloxy-4-chloro-6-methoxy-quinoline
• Synonyms: 7-Benzyloxy-4-chloro-6-methoxy-quinoline;4-Chloro-6-methoxy-7-benzyloxyquinoline;Quinoline, 4-chloro-6-Methoxy-7-(phenylMethoxy)-;4-chloro-6-methoxy-7-phenylmethoxyquinoline;7-(Benzyloxy)
• CAS NO: 286371-49-1
• Molecular Formula: C₁₇H₁₄ClNO₂
• Molecular Weight: 299.75156
• EINECS: 1592732-453-0
• Mol File: 286371-49-1.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 434.8±40.0 °C(Predicted)
• Appearance: /
• Density: 1.262
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 3.92±0.30(Predicted)
• CAS DataBase Reference: 7-Benzyloxy-4-chloro-6-methoxy-quinoline(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Benzyloxy-4-chloro-6-methoxy-quinoline(286371-49-1)
• EPA Substance Registry System: 7-Benzyloxy-4-chloro-6-methoxy-quinoline(286371-49-1)

Safety Data

• Hazardous Substances Data: 286371-49-1(Hazardous Substances Data)

Usage

Uses

7-(benzyloxy)-4-chloro-6-methoxyquinoline (cas# 286371-49-1) is a useful research chemical.

Synthetic route

4-hydroxy-6-methoxy-7-benzyloxyquinoline (205448-29-9, 849217-23-8) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Stage #1: 7-benzyloxy-4-hydroxy-6-methoxyquinoline With trichlorophosphate for 2h; Heating / reflux; Stage #2: With sodium hydrogencarbonate; sodium carbonate In water at 20℃; pH=8;	95%
With trichlorophosphate for 2h; Heating / reflux;	95%
With trichlorophosphate In toluene at 120℃; for 1.5h;	90%

4-chloro-6-methoxy-7-hydroxyquinoline (205448-31-3) + benzyl bromide (100-39-0) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 45℃; for 2h;	95%

6-methoxy-7-benzyloxy-4(1H)-quinolinone (205448-29-9, 849217-23-8) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Stage #1: 6-methoxy-7-benzyloxy-4(1H)-quinolinone With trichlorophosphate at 110℃; for 3h; Stage #2: With sodium carbonate In chloroform; water Cooling with ice;	94%
With sodium hydroxide; trichlorophosphate In chloroform	21%
With trichlorophosphate In acetonitrile for 6h; Reflux;	174.8 g

1-(2-amino-4-(benzyloxy)-5-methoxyphenyl)ethanone (75665-73-5) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium methylate / Dimethyl ether / 0.5 h / 20 °C 1.2: 8 h 2.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: sodium methylate / 1,2-dimethoxyethane / 0.5 h / Inert atmosphere 1.2: Inert atmosphere 2.1: trichlorophosphate / 10 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: sodium methylate / 1,2-dimethoxyethane / 0.5 h 1.2: 15 h / 20 °C 2.1: trichlorophosphate / 4.33 h / Cooling with ice; Reflux View Scheme

benzyl bromide (100-39-0) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 40 °C 2.1: nitric acid; sulfuric acid / dichloromethane / 1 h / 0 °C / pH 7 - 8 3.1: ammonium formate; iron / toluene; water / 103 °C 4.1: sodium methylate / Dimethyl ether / 0.5 h / 20 °C 4.2: 8 h 5.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 40 °C 2.1: nitric acid; sulfuric acid / dichloromethane / 2.25 h / 0 °C 3.1: iron; ammonium acetate / toluene; water / 105 °C 4.1: sodium methylate / 1,2-dimethoxyethane / 0.5 h / Inert atmosphere 4.2: Inert atmosphere 5.1: trichlorophosphate / 10 h / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 4 h / 20 °C 2.1: nitric acid / dichloromethane / 2 h / -20 - -10 °C 3.1: 5,5-dimethyl-1,3-cyclohexadiene / 15 h / Reflux 4.1: iron; acetic acid / 2 h / 60 - 90 °C 5.1: trichlorophosphate / acetonitrile / 6 h / Reflux View Scheme

4-benzyloxy-3-methoxyacetophenone (1835-11-6) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: nitric acid; sulfuric acid / dichloromethane / 1 h / 0 °C / pH 7 - 8 2.1: ammonium formate; iron / toluene; water / 103 °C 3.1: sodium methylate / Dimethyl ether / 0.5 h / 20 °C 3.2: 8 h 4.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: nitric acid; sulfuric acid / dichloromethane / 2.25 h / 0 °C 2.1: iron; ammonium acetate / toluene; water / 105 °C 3.1: sodium methylate / 1,2-dimethoxyethane / 0.5 h / Inert atmosphere 3.2: Inert atmosphere 4.1: trichlorophosphate / 10 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: nitric acid / dichloromethane / 2 h / -20 - -10 °C 2: 5,5-dimethyl-1,3-cyclohexadiene / 15 h / Reflux 3: iron; acetic acid / 2 h / 60 - 90 °C 4: trichlorophosphate / acetonitrile / 6 h / Reflux View Scheme

1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone (75665-88-2) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ammonium formate; iron / toluene; water / 103 °C 2.1: sodium methylate / Dimethyl ether / 0.5 h / 20 °C 2.2: 8 h 3.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: iron; ammonium acetate / toluene; water / 105 °C 2.1: sodium methylate / 1,2-dimethoxyethane / 0.5 h / Inert atmosphere 2.2: Inert atmosphere 3.1: trichlorophosphate / 10 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: 5,5-dimethyl-1,3-cyclohexadiene / 15 h / Reflux 2: iron; acetic acid / 2 h / 60 - 90 °C 3: trichlorophosphate / acetonitrile / 6 h / Reflux View Scheme

1-(3-methoxy-4-hydroxyphenyl)ethanone (498-02-2) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 40 °C 2.1: nitric acid; sulfuric acid / dichloromethane / 1 h / 0 °C / pH 7 - 8 3.1: ammonium formate; iron / toluene; water / 103 °C 4.1: sodium methylate / Dimethyl ether / 0.5 h / 20 °C 4.2: 8 h 5.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 40 °C 2.1: nitric acid; sulfuric acid / dichloromethane / 2.25 h / 0 °C 3.1: iron; ammonium acetate / toluene; water / 105 °C 4.1: sodium methylate / 1,2-dimethoxyethane / 0.5 h / Inert atmosphere 4.2: Inert atmosphere 5.1: trichlorophosphate / 10 h / Reflux View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 4 h / 20 °C 2.1: nitric acid / dichloromethane / 2 h / -20 - -10 °C 3.1: 5,5-dimethyl-1,3-cyclohexadiene / 15 h / Reflux 4.1: iron; acetic acid / 2 h / 60 - 90 °C 5.1: trichlorophosphate / acetonitrile / 6 h / Reflux View Scheme

5-{[(3-(benzyloxy)-4-methoxyphenyl)amino]methylene}-2,2-dimethyl-1,3-dioxane-4,6- dione (205448-28-8) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: biphenyl / diphenylether / 1 h / 220 °C / Inert atmosphere 2: trichlorophosphate / 5 h / Inert atmosphere; Reflux View Scheme
Multi-step reaction with 2 steps 1: 1,2-dichloro-benzene / 7 h / 180 °C 2: trichlorophosphate / toluene / 1.5 h / 120 °C View Scheme
Multi-step reaction with 2 steps 1: 1,2-dichloro-benzene / 7 h / 180 °C 2: trichlorophosphate / N,N-dimethyl-formamide / 1 h / 100 °C View Scheme

1-[2-nitro-4-benzyloxy-5-methoxyphenyl]-3-(dimethylamino)prop-2-en-1-one → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: iron; acetic acid / 2 h / 60 - 90 °C 2: trichlorophosphate / acetonitrile / 6 h / Reflux View Scheme

2-(benzyloxy)-1-methoxy-4-nitrobenzene (75167-86-1) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium chloride; iron / ethanol; water / 1 h / 20 °C / Reflux 2: ethanol / 1 h / Reflux 3: 1,2-dichloro-benzene / 7 h / 180 °C 4: trichlorophosphate / toluene / 1.5 h / 120 °C View Scheme
Multi-step reaction with 4 steps 1: iron / ethanol; water / Reflux 2: ethanol / 1 h / 80 °C 3: 1,2-dichloro-benzene / 7 h / 180 °C 4: trichlorophosphate / N,N-dimethyl-formamide / 1 h / 100 °C View Scheme

3-benzyloxy-4-methoxybenzeneamine (61324-40-1) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / 1 h / Reflux 2: 1,2-dichloro-benzene / 7 h / 180 °C 3: trichlorophosphate / toluene / 1.5 h / 120 °C View Scheme
Multi-step reaction with 3 steps 1: ethanol / 1 h / 80 °C 2: 1,2-dichloro-benzene / 7 h / 180 °C 3: trichlorophosphate / N,N-dimethyl-formamide / 1 h / 100 °C View Scheme

5-nitroguaiacol (636-93-1) → 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 40 °C 2: ammonium chloride; iron / ethanol; water / 1 h / 20 °C / Reflux 3: ethanol / 1 h / Reflux 4: 1,2-dichloro-benzene / 7 h / 180 °C 5: trichlorophosphate / toluene / 1.5 h / 120 °C View Scheme
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 90 °C 2: iron / ethanol; water / Reflux 3: ethanol / 1 h / 80 °C 4: 1,2-dichloro-benzene / 7 h / 180 °C 5: trichlorophosphate / N,N-dimethyl-formamide / 1 h / 100 °C View Scheme

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 4-chloro-6-methoxy-7-hydroxyquinoline (205448-31-3)

Conditions	Yield
With methanesulfonic acid; trifluoroacetic acid for 3h; Reflux; Inert atmosphere;	100%
Stage #1: 7-(benzyloxy)-4-chloro-6-methoxyquinoline With methanesulfonic acid; trifluoroacetic acid for 3h; Reflux; Stage #2: With sodium hydroxide for 2h; pH=7;	100%
With trifluoroacetic acid at 75℃; for 6h;	95.4%
With hydrogen bromide; acetic acid In water at 80℃; for 3h;	80%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 4-Amino-3-chlorophenol hydrochloride (52671-64-4) → 4-{[7-(Benzyloxy)-6-methoxy-4-quinolyl]oxy}-2-chloroaniline (286371-53-7)

Conditions	Yield
With sodium hydride; potassium carbonate In N,N-dimethyl-formamide; mineral oil at 100℃; for 2h; Inert atmosphere;	98%
With dimethyl sulfoxide In methanol; water	66%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 4-(7-benzyloxy-6-methoxyquinolin-4-yloxy)aniline (516526-32-2)

Conditions	Yield
Stage #1: 4-amino-phenol With sodium methylate In methanol; ISOPROPYLAMIDE at 20℃; for 1h; Stage #2: 7-(benzyloxy)-4-chloro-6-methoxyquinoline In ISOPROPYLAMIDE at 120℃; for 22h;	96%
Multi-step reaction with 2 steps 1.1: 1-methyl-pyrrolidin-2-one / 2 h / 150 °C 2.1: hydrogenchloride; methanol; water / 6 h / Heating / reflux 2.2: pH 12 View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 5,5-dimethyl-1,3-cyclohexadiene / 140 °C / Inert atmosphere 2: iron; ammonium chloride / ethanol; water / 2 h / 90 °C / Inert atmosphere View Scheme

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 2-fluoro-4-nitrophenol (403-19-0) → 7-benzyloxy-4-(2-fluoro-4-nitro-phenoxy)-6-methyloxyquinoline (479690-03-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In chlorobenzene at 140℃; for 18h;	92%
With N-ethyl-N,N-diisopropylamine In chlorobenzene for 48h; Reflux;	82%
With N-ethyl-N,N-diisopropylamine In 5,5-dimethyl-1,3-cyclohexadiene at 140℃;	81%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + ethyl 1-[(3-fluoro-4-hydroxyphenyl)carbamoyl]cyclopropane-1-carboxylate → ethyl 1-[[3-fluoro-4-[[6-methoxy-7-benzyloxyquinolin-4-yl]oxy]phenyl]carbamoyl]cyclopropane-1-carboxylate

Conditions	Yield
With dmap at 160℃; for 4h;	90.5%

4-nitro-phenol (100-02-7) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 7-(benzyloxy)-6-methoxy-4-(4-nitrophenoxy)quinoline (417725-03-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In xylene for 12h; Reflux;	84.3%
In chlorobenzene for 16h; Reflux;	62.4%
In chlorobenzene for 20h; Reflux;	201.8 g

1-(2-fluoro-3-hydroxy-6-nitrophenyl)propan-2-one (649736-31-2) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 1-(3-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-2-fluoro-6-nitrophenyl)propan-2-one (1210828-42-4)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In 1-methyl-pyrrolidin-2-one at 100℃;	84%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 3-fluoro-4-nitrophenol (394-41-2) → 7-(benzyloxy)-4-(3-fluoro-4-nitrophenoxy)-6-methoxyquinoline (286371-58-2)

Conditions	Yield
In chlorobenzene at 120℃; for 21h;	82%
Stage #1: 7-(benzyloxy)-4-chloro-6-methoxyquinoline; 3-fluoro-4-nitrophenol In chlorobenzene at 120℃; for 21h; Stage #2: With sodium hydroxide In chloroform; water; chlorobenzene at 20℃;	82%
With N-ethyl-N,N-diisopropylamine In chlorobenzene at 140℃; for 15h;	50%
With sodium hydroxide In chloroform; chlorobenzene	47%
In chlorobenzene for 16h; Reflux;

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + methyl-phenyl-thioether (100-68-5) → 4-chloro-6-methoxy-7-hydroxyquinoline (205448-31-3)

Conditions	Yield
With sodium hydroxide; methanesulfonic acid In hexane; trifluorormethanesulfonic acid	75%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 4-amino-2-fluorophenol (399-96-2) → 4-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-3-fluorobenzenamine (479690-04-5)

Conditions	Yield
Stage #1: 4-amino-2-fluorophenol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5h; Inert atmosphere; Stage #2: 7-(benzyloxy)-4-chloro-6-methoxyquinoline In N,N-dimethyl-formamide; mineral oil at 100℃; for 30h;	73%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + N-(3-fluoro-4-hydroxyphenyl)-N'-(2-phenylethyl)ethanediamide (849217-56-7) → N-{4-[(7-benzyloxy-6-methoxyquinolin-4-yl)oxy]-3-fluorophenyl}-N'-(2-phenylethyl)ethanediamide

Conditions	Yield
With dmap; bromobenzene for 6h; Heating / reflux;	61%
With dmap In bromobenzene for 6h; Heating / reflux;	61%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + para-nitrobenzenethiol (1849-36-1) → 7-(benzyloxy)-6-methoxy-4-((4-nitrophenyl)thio)quinoline

Conditions	Yield
In chlorobenzene for 16h; Reflux;	60.1%

6-hydroxy-N-methyl-1-naphthalenecarboxamide (847802-91-9) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 6-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (1058137-70-4)

Conditions	Yield
With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide; acetylacetone at 120℃; for 24h; Reagent/catalyst; Solvent; Temperature; Time; Concentration;	58%
With dmap In 1,4-dioxane for 72h; Product distribution / selectivity; Heating / reflux;

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + meta-nitrophenol (554-84-7) → C23H18N2O5

Conditions	Yield
In chlorobenzene for 16h; Reflux;	52.4%
In chlorobenzene for 18h; Reflux;

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 2,5-dimethyl-4-amino phenol (3096-71-7) → 4-{[7-(Benzyloxy)-6-methoxy-4-quinolyl]oxy}-2,5-dimethylaniline (286371-50-4)

Conditions	Yield
With dimethyl sulfoxide In methanol; water	52%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 4-amino-2,3-dimethylphenol (3096-69-3) + sodium hydrogencarbonate (144-55-8) → 4-{[7-(Benzyloxy)-6-methoxy-4-quinolyl]oxy}-2,3-dimethylaniline (286371-56-0)

Conditions	Yield
With dimethyl sulfoxide	49%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 2-phenyl-[1,8]naphthyridin-3-ol (666735-37-1) → 3-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-2-phenyl-[1,8]naphthyridine

Conditions	Yield
With dmap In 1,2-dichloro-benzene at 140℃; for 20h;	42%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-ol hydrochloride (1149370-96-6) → 7-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine (1149370-97-7)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 109h;	40.5%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + thiophene-2-carboxylic acid (4-hydroxy-phenyl)-amide (98902-53-5) → thiophene-2-carboxylic acid [4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-amide (914490-48-5)

Conditions	Yield
In N,N-dimethyl-formamide at 140℃; for 5h;	36%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + p-benzoylaminophenol (15457-50-8) → N-[4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-benzamide (914200-89-8)

Conditions	Yield
at 140℃; for 3h;	32%
at 140℃; for 3h; Product distribution / selectivity;	32%
at 140℃; for 3h;	32%
In N,N-dimethyl-formamide at 145℃; for 7h; Product distribution / selectivity;	28%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 7-(benzyloxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinoline (1210828-43-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 100℃; for 16h; Inert atmosphere;	27%
With dmap In 1,4-dioxane for 72h; Reflux;

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 2-(4-hydroxyphenyl)-1-phenylethan-1-one (6420-90-2) → 2-[4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-1-phenyl-ethanone (914490-65-6)

Conditions	Yield
In N,N-dimethyl-formamide at 145℃; for 5h;	21%

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + sodium 4-aminophenolate (15267-98-8) → 4-(7-benzyloxy-6-methoxyquinolin-4-yloxy)aniline (516526-32-2)

Conditions	Yield
In ISOPROPYLAMIDE at 120℃; for 22h;

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 4-acetaminophenol (103-90-2) → N-[4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-acetamide (914490-52-1)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 150℃; for 2h;

7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) + 6-hydroxy-1-naphthoic acid (2437-17-4) → 6-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-1-naphthoic acid (1044676-75-6)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 130℃; for 5h;

indol-5-ol (1953-54-4) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → C25H20N2O3 (1058157-84-8)

Conditions	Yield
With dmap In 1,4-dioxane for 72h; Heating / reflux;

5-amino-1H-indole (5192-03-0) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 4-(1H-indol-5-ylamino)-7-benzyloxy-6-methoxy-quinoline (1058157-22-4)

Conditions	Yield
In isopropyl alcohol for 1h; Heating / reflux;

Upstream product

• 100-39-0 benzyl bromide 
• 1835-11-6 4-benzyloxy-3-methoxyacetophenone 
• 75665-88-2 1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone 
• 498-02-2 1-(3-methoxy-4-hydroxyphenyl)ethanone 
• 636-93-1 5-nitroguaiacol 
• 61324-40-1 3-benzyloxy-4-methoxybenzeneamine 
• 75167-86-1 2-(benzyloxy)-1-methoxy-4-nitrobenzene 
• 205448-28-8 5-{[(3-(benzyloxy)-4-methoxyphenyl)amino]methylene}-2,2-dimethyl-1,3-dioxane-4,6- dione 
• 205448-31-3 4-chloro-6-methoxy-7-hydroxyquinoline 
• 75665-73-5 1-(2-amino-4-(benzyloxy)-5-methoxyphenyl)ethanone 
• 205448-29-9 6-methoxy-7-benzyloxy-4(1H)-quinolinone 
• 205448-29-9 7-benzyloxy-4-hydroxy-6-methoxyquinoline 

Downstream Products

• 914200-89-8 N-[4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-benzamide 
• 914490-52-1 N-[4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-acetamide 
• 914490-48-5 thiophene-2-carboxylic acid [4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-phenyl]-amide 
• 205448-31-3 4-chloro-6-methoxy-7-hydroxyquinoline 
• 1058137-70-4 6-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide 
• 1044676-75-6 6-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-1-naphthoic acid 
• 1058157-84-8 C₂₅H₂₀N₂O₃ 
• 1058157-22-4 4-(1H-indol-5-ylamino)-7-benzyloxy-6-methoxy-quinoline 
• 861881-04-1 4-chloro-7-(3-chloropropoxy)-6-methoxyquinoline 
• 1622396-60-4 C₂₆H₃₀ClN₃O₄ 
• 1622396-74-0 C₂₄H₂₀FN₃O₄ 
• 1622396-75-1 C₃₀H₂₉ClFN₃O₆ 
• 1622396-76-2 C₃₀H₃₀FN₃O₆ 
• 1622396-77-3 C₂₈H₂₅ClFN₃O₆ 

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Discovery of 1,6-naphthyridinone-based MET kinase inhibitor bearing quinoline moiety as promising antitumor drug candidate

A series of 1,6-naphthyridinone-based MET kinase inhibitors bearing quinoline moiety in block A were designed and synthesized based on the structures of Cabozantinib and our reported compound IV. Extensive SAR and DMPK studies led to the identification of 20j, a potent and orally bioavailable MET kinase inhibitor with favorable kinase selectivity. More importantly, 20j exhibited statistically significant tumor growth inhibition (Tumor growth inhibition/TGI of 131%, 4/6 partial regression/PR) in the U-87 MG xeograft model, which is superior to that of Cabozantinib (TGI of 97%, 2/6 PR), and significantly better than that of compound IV (TGI of 15%, 0/6 PR) at the same dose (12.5 mg/kg). Combined with favorable in vitro potency, kinase selectivity, pharmacokinetic profile and in vivo efficacy, the promising antitumor drug candidate 20j has subsequently advanced into preclinical research.

CARBAMATE AND UREA COMPOUNDS AS MULTIKINASE INHIBITORS

The present disclosure describes carbamate and urea compounds as novel multikinase inhibitors and methods for preparing them. The pharmaceutical compositions comprising such multikinase inhibitors and methods of using them for treating cancer, infectious diseases, and other disorders associated with kinases are also described.

Naphthyridine compound and pharmaceutical composition as well as applications thereof

The invention relates to the field of biological medicines and discloses a naphthyridine compound and a pharmaceutical composition as well as applications thereof. The naphthyridine compound has a structure shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, hydrate, solvate, metabolite, a pharmaceutically acceptable salt or a prodrug. The naphthyridine compound disclosed by the invention has an anti-tumor effect which is obviously superior to the anti-tumor effect of the prior art. And moreover, the naphthyridine compound disclosed by the invention can treat diseases mediated by protein kinase.