5498-31-7

Basic information

• Product Name: 4-bromonaphthalen-2-ol
• Synonyms: 4-bromonaphthalen-2-ol;1-Bromo-3-hydroxynaphthalene
• CAS NO: 5498-31-7
• Molecular Formula: C₁₀H₇BrO
• Molecular Weight: 223.06598
• Mol File: 5498-31-7.mol
• Article Data: 18

Chemical Properties

• Melting Point: 122 °C
• Boiling Point: 346.8±15.0 °C(Predicted)
• Appearance: /
• Density: 1.614±0.06 g/cm3(Predicted)
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 8.76±0.40(Predicted)
• CAS DataBase Reference: 4-bromonaphthalen-2-ol(CAS DataBase Reference)
• NIST Chemistry Reference: 4-bromonaphthalen-2-ol(5498-31-7)
• EPA Substance Registry System: 4-bromonaphthalen-2-ol(5498-31-7)

Safety Data

• Hazardous Substances Data: 5498-31-7(Hazardous Substances Data)

Usage

Uses

4-Bromo-2-naphthalenol is used as a reactant in the preparation of pyrazoles as inhibitors of macrophage migration inhibitory factor.

Synthetic route

4-bromo-1-diazonio-naphthalen-2-olate (33670-68-7) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
With sodium tetrahydroborate In ethanol at 0℃; for 3h;	98%
With sodium tetrahydroborate In ethanol at 0℃; for 3h;	98%
With ethanol; aluminium

5-bromonaphtho[1,2-d][1,2,3]oxadiazole → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Stage #1: 5-bromonaphtho[1,2-d][1,2,3]oxadiazole With sodium tetrahydroborate; ethanol for 12h; Inert atmosphere; Stage #2: With hydrogenchloride In water for 1h;	78%
With sodium tetrahydroborate; ethanol for 12h; Inert atmosphere;	78%
Stage #1: 5-bromonaphtho[1,2-d][1,2,3]oxadiazole With sodium tetrahydroborate; ethanol for 12h; Inert atmosphere; Stage #2: With hydrogenchloride In water for 1h;	78%
Stage #1: 5-bromonaphtho[1,2-d][1,2,3]oxadiazole With sodium tetrahydroborate; ethanol for 12h; Inert atmosphere; Stage #2: With hydrogenchloride; water for 1h;	78%
Stage #1: 5-bromonaphtho[1,2-d][1,2,3]oxadiazole With sodium tetrahydroborate In ethanol for 12h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; water for 1h; Inert atmosphere;	78%

4-bromo-2-hydroxynaphthalene-1-diazonium salt (53846-22-3) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
With sodium tetrahydroborate In ethanol at 0 - 10℃;	75%

4-bromo-2-hydroxynaphthalene-1-diazonium bromide → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
With sodium tetrahydroborate; ethanol at 10 - 20℃; for 1.5h;	37%

4-bromonaphthalen-2-amine (74924-94-0) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
With sulfuric acid; Methamphetamin Diazotization.anschliessendes Erwaermen;
(i) NaNO2, (ii) aq. H2SO4; Multistep reaction;

4-bromo-2-nitro-1-naphthylamine (90767-01-4) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid; nitrosylhydrogen sulfate 2: aluminium-powder; ethanol View Scheme
Multi-step reaction with 3 steps 1: (i) NaNO2, (ii) (deamination) 2: (reduction) 3: (i) NaNO2, (ii) aq. H2SO4 View Scheme

1-bromo-3-nitronaphthalene (7499-65-2) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: (reduction) 2: (i) NaNO2, (ii) aq. H2SO4 View Scheme

1-amino-naphthalene (134-32-7) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine; acetic acid / 1 h / 70 °C 2: acetic acid; propionic acid; sodium nitrite / 1 h / 5 - 8 °C 3: sodium tetrahydroborate / ethanol / 4 h / 13 - 18 °C View Scheme
Multi-step reaction with 3 steps 1: acetic acid; bromine / 0.33 h / 0 - 60 °C 2: acetic acid; sodium nitrite / propionic acid / 0.17 h / 0 °C 3: sodium tetrahydroborate / ethanol / 3 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: bromine; acetic acid / 1 h / 70 °C 2: propionic acid; acetic acid; sodium nitrite / 1 h / 5 - 8 °C 3: sodium tetrahydroborate; ethanol / 4 h / 13 - 18 °C View Scheme

2,4-dibromo-1-naphthylamine (20191-76-8) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; propionic acid; sodium nitrite / 1 h / 5 - 8 °C 2: sodium tetrahydroborate / ethanol / 4 h / 13 - 18 °C View Scheme
Multi-step reaction with 2 steps 1: acetic acid; sodium nitrite / propionic acid / 0.17 h / 0 °C 2: sodium tetrahydroborate / ethanol / 3 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: propionic acid; acetic acid; sodium nitrite / 1 h / 5 - 8 °C 2: sodium tetrahydroborate; ethanol / 4 h / 13 - 18 °C View Scheme

6-methoxy-3,4-dihydro-1(2H)-naphthalenone (1078-19-9) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: pyridine / ethanol / 16 h / 20 °C 2.1: acetic acid; palladium diacetate; N-Bromosuccinimide / 1 h / 80 °C 3.1: hydrogenchloride / 1,4-dioxane / 1 h / Reflux 4.1: sodium tetrahydroborate; ethanol / 16 h / 0 - 20 °C 5.1: toluene-4-sulfonic acid / toluene / 0.5 h / 0 °C / Reflux 5.2: 2 h / 40 °C 5.3: 16 h / 0 - 20 °C View Scheme

(N,6-dimethoxy-3,4-dihydro-2H-naphthalen-1-imine) (945830-92-2) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: acetic acid; palladium diacetate; N-Bromosuccinimide / 1 h / 80 °C 2.1: hydrogenchloride / 1,4-dioxane / 1 h / Reflux 3.1: sodium tetrahydroborate; ethanol / 16 h / 0 - 20 °C 4.1: toluene-4-sulfonic acid / toluene / 0.5 h / 0 °C / Reflux 4.2: 2 h / 40 °C 4.3: 16 h / 0 - 20 °C View Scheme

C12H14BrNO2 → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / 1,4-dioxane / 1 h / Reflux 2.1: sodium tetrahydroborate; ethanol / 16 h / 0 - 20 °C 3.1: toluene-4-sulfonic acid / toluene / 0.5 h / 0 °C / Reflux 3.2: 2 h / 40 °C 3.3: 16 h / 0 - 20 °C View Scheme

C10H9BrO2 → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Stage #1: C10H9BrO2 With toluene-4-sulfonic acid In toluene at 0℃; for 0.5h; Reflux; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone; potassium hydroxide In toluene at 40℃; for 2h; Stage #3: With boron tribromide In dichloromethane at 0 - 20℃; for 16h;

8-bromo-6-methoxy-3,4-dihydronaphthalen-1(2H)-one → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate; ethanol / 16 h / 0 - 20 °C 2.1: toluene-4-sulfonic acid / toluene / 0.5 h / 0 °C / Reflux 2.2: 2 h / 40 °C 2.3: 16 h / 0 - 20 °C View Scheme

2,3-dibromonaphthalene-1-amine → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetic acid; sodium nitrite; propionic acid / 0.5 h / 0 °C 2.1: sodium tetrahydroborate; ethanol / 12 h / Inert atmosphere 2.2: 1 h View Scheme
Multi-step reaction with 2 steps 1.1: acetic acid; sodium nitrite; propionic acid / 0.5 h / 0 °C 2.1: sodium tetrahydroborate; ethanol / 12 h / Inert atmosphere 2.2: 1 h View Scheme
Multi-step reaction with 2 steps 1.1: acetic acid; propionic acid / 0 °C 1.2: 0.5 h 2.1: sodium tetrahydroborate; ethanol / 12 h / Inert atmosphere 2.2: 1 h View Scheme

1-Nitronaphthalene (86-57-7) → 4-bromo-naphthalen-2-ol (5498-31-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylsilane; palladium dichloride / ethanol / 0.17 h / Inert atmosphere 2: bromine / acetic acid / 0.25 h / 0 - 60 °C 3: sodium nitrite; acetic acid; propionic acid / 0.17 h / 8 - 10 °C 4: sodium tetrahydroborate / ethanol / 0 - 10 °C View Scheme

4-bromo-naphthalen-2-ol (5498-31-7) → 4,4'-dibromo-[1,1'-binaphthalene]-2,2'-diol (178065-22-0, 178065-27-5, 178065-28-6)

Conditions	Yield
With di-μ-hydroxo-bis[(N,N,N′,N′-tetramethylethylenediamine)copper(II)] chloride In dichloromethane at 20℃; for 16h;	100%
With oxygen In dichloromethane	90%
With N,N,N,N,-tetramethylethylenediamine; oxygen In dichloromethane at 25℃; for 4h;	90%

4-bromo-naphthalen-2-ol (5498-31-7) + methyl iodide (74-88-4) → 1-bromo-3-methoxy-naphthalene (5111-34-2)

Conditions	Yield
Stage #1: 4-bromo-naphthalen-2-ol With sodium hydride In N,N-dimethyl-formamide; mineral oil Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 20℃; for 3h;	97%

triisopropylsilyl chloride (13154-24-0) + 4-bromo-naphthalen-2-ol (5498-31-7) → 4-Bromo-2-triisopropylsiloxynaphthalene (1186084-72-9)

Conditions	Yield
Stage #1: 4-bromo-naphthalen-2-ol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: triisopropylsilyl chloride In tetrahydrofuran at 0 - 20℃; for 2h;	96%

4-bromo-naphthalen-2-ol (5498-31-7) + benzyl bromide (100-39-0) → 3-(benzyloxy)-1-bromonaphthalene (611235-22-4)

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 1h;	95%
With potassium carbonate In acetonitrile at 80℃; for 1h;	95%
Stage #1: 4-bromo-naphthalen-2-ol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 50℃; for 1h; Inert atmosphere; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide at 20℃; for 16h; Inert atmosphere;	93%

4-bromo-naphthalen-2-ol (5498-31-7) + tert-butyldimethylsilyl chloride (18162-48-6) → (4-bromo-2-naphthyl)oxy-tert-butyldimethyl-silane

Conditions	Yield
With 1H-imidazole In dichloromethane at 25℃; for 1h;	90.7%

4-bromo-naphthalen-2-ol (5498-31-7) + diphenylamine (122-39-4) → 4-(diphenylamino)naphthalen-2-ol

Conditions	Yield
With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); sodium t-butanolate In toluene for 4h; Inert atmosphere; Reflux;	89.5%

4-bromo-naphthalen-2-ol (5498-31-7) + Diphenylphosphinic chloride (1499-21-4) → diphenyl-phosphinic acid 4-bromo-naphthalen-2-yl ester (864423-16-5)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 18h;	88%

trifluoromethylsulfonic anhydride (358-23-6) + 4-bromo-naphthalen-2-ol (5498-31-7) → 4-bromonaphthalen-2-yl trifluoromethanesulfonate

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃;	86.7%
With pyridine In dichloromethane at 0 - 20℃;	86.7%
With pyridine In dichloromethane at 0 - 20℃;	86.7%
With pyridine In dichloromethane at 0 - 20℃;	86.7%

4-bromo-naphthalen-2-ol (5498-31-7) + (3-(chloro(3,5-dimethylphenyl)phosphoryl)-5-methylphenyl)methylium (137219-83-1) → C26H24BrO2P (1198163-29-9)

Conditions	Yield
With dmap; triethylamine In dichloromethane	85%

4-bromo-naphthalen-2-ol (5498-31-7) + 2-bromo-1-(triisopropylsilyloxy)ethane (425638-79-5) → [2-(4-bromonaphthalen-2-yloxy)ethoxy]triisopropylsilane (1191399-68-4)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 60℃; for 5h;	84%
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N-methyl-acetamide

4-bromo-naphthalen-2-ol (5498-31-7) + acetyl chloride (75-36-5) → 1-(4-bromo-2-hydroxynapthalen-1-yl)ethanone (838855-57-5)

Conditions	Yield
With aluminum (III) chloride In dichloromethane for 2h; Heating / reflux;	83%

4-bromo-naphthalen-2-ol (5498-31-7) + chloromethyl methyl ether (107-30-2) → 1-bromo-3-(methoxymethoxy)naphthalene

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 14h;	81%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 14h;	81%
Stage #1: 4-bromo-naphthalen-2-ol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Stage #2: chloromethyl methyl ether In tetrahydrofuran; mineral oil at 20℃; for 3h;	72%
With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	43%

4-bromo-naphthalen-2-ol (5498-31-7) → C10H6BrIO

Conditions	Yield
Stage #1: 4-bromo-naphthalen-2-ol With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: With iodine In tetrahydrofuran at 20℃;	75%

4-bromo-naphthalen-2-ol (5498-31-7) + phenylboronic acid (98-80-6) → 4-phenylnaphthalen-2-ol (36159-74-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 65℃; for 18h;	73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 65℃; for 18h;	73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 65℃; for 18h;	73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 65℃; for 18h;	73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran at 65℃; for 18h;	72%

2-pyrazylcarboxylic acid (98-97-5) + 4-bromo-naphthalen-2-ol (5498-31-7) → C15H9BrN2O2

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbamide; 4-<3-(dimethylamino)propyl>pyridine In tetrahydrofuran at 20℃; for 24h;	72%

4-bromo-naphthalen-2-ol (5498-31-7) + 2,4-diphenyl-6-(4-(4,4',5,5'-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1,3,5-triazine → C31H21N3O

Conditions	Yield
With bis(tri-t-butylphosphine)palladium(0); potassium carbonate In tetrahydrofuran; water for 12h; Inert atmosphere; Reflux;	71%

4-bromo-naphthalen-2-ol (5498-31-7) + 1,1-diphenyl-2-propyn-1-ol (3923-52-2) → 6-bromo-3,3-diphenyl-<3H>-naphtho<2,1-b>pyran (227471-77-4)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane Ambient temperature;	67%
With toluene-4-sulfonic acid In dichloromethane at 20℃; for 12h;	67%

4-bromo-naphthalen-2-ol (5498-31-7) + bis(pinacol)diborane (73183-34-3) → 4-(4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl)naphthalen-2-ol

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	67%

4-bromo-naphthalen-2-ol (5498-31-7) + pivaloyl chloride (3282-30-2) → (4-bromo-2-naphthyl) 2,2-dimethylpropanoate

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 0.0166667h;	65.4%
With triethylamine In dichloromethane at 0℃; for 0.166667h;	65.4%
With triethylamine In dichloromethane at 0℃; for 0.166667h;	65.4%
With triethylamine In dichloromethane at 0℃; for 0.166667h;	64.4%

10-phenylanthracene-9-boronic acid + 4-bromo-naphthalen-2-ol (5498-31-7) → C30H20O

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water; toluene at 110℃;	64.7%

4-bromo-naphthalen-2-ol (5498-31-7) + 5,5-dimethyl-2-(thiophen-2-yl)-1,3,2-dioxaborinane (355408-55-8) → 4-(thien-2-yl)naphth-2-ol

Conditions	Yield
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 100℃; for 20h;	54%

4-bromo-naphthalen-2-ol (5498-31-7) + 5,5-dimethyl-2-(2,2'-bithien-5-yl)[1,3,2]dioxoborinane (320381-92-8) → 4-(2,2'-bithien-5-yl)naphth-2-ol (583886-91-3)

Conditions	Yield
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 100℃; for 20h;	49%

4-bromo-naphthalen-2-ol (5498-31-7) + dimethyl sulfate (77-78-1) → 1-bromo-3-methoxy-naphthalene (5111-34-2)

Conditions	Yield
With sodium hydroxide In water at 20℃; for 24h;	41%
With sodium hydroxide In water for 24h;	41%
With hydroxide

benzenediazonium (2684-02-8) + 4-bromo-naphthalen-2-ol (5498-31-7) → 4-bromo-1-phenylazo-[2]naphthol

p-nitrobenzenediazonium (14368-49-1) + 4-bromo-naphthalen-2-ol (5498-31-7) → 4-bromo-1-(4-nitro-phenylazo)-[2]naphthol

4-bromo-naphthalen-2-ol (5498-31-7) + 2-hydroxy-2-phenylacetophenone (119-53-9) → 5-bromo-1,2-diphenyl-naphtho[2,1-b]furan (873965-31-2)

Conditions	Yield
With sulfuric acid

Upstream product

• 86-57-7 1-Nitronaphthalene 
• 53846-22-3 4-bromo-2-hydroxynaphthalene-1-diazonium salt 
• 172943-00-9 5-bromonaphtho[1,2-d][1,2,3]oxadiazole 
• 945830-92-2 (N,6-dimethoxy-3,4-dihydro-2H-naphthalen-1-imine) 
• 1078-19-9 6-methoxy-3,4-dihydro-1(2H)-naphthalenone 
• 20191-76-8 2,4-dibromo-1-naphthylamine 
• 134-32-7 1-amino-naphthalene 
• 7499-65-2 4-bromo-2-nitronaphthalene 
• 90767-01-4 4-bromo-2-nitro-1-naphthylamine 
• 74924-94-0 4-bromonaphthalene-2-amine 
• 33670-68-7 4-bromo-1-diazonio-naphthalen-2-olate 

Downstream Products

• 91136-43-5 3-hydroxynaphthalenecarboxaldehyde 
• 227471-77-4 6-bromo-3,3-diphenyl-<3H>-naphtho<2,1-b>pyran 
• 2374831-10-2 ethyl 3-(3-methoxy-1-naphthylamino)benzoate 
• 74924-94-0 4-bromonaphthalene-2-amine 
• 2043962-01-0 4-(4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl)naphthalen-2-ol 
• 838855-58-6 1-[2-hydroxy-4-(4-hydroxyphenyl)napthalen-1-yl]ethanone 
• 838855-56-4 4-(1-methyl-3H-benzo[e]indazol-5-yl)phenol 
• 2158303-49-0 1-bromo-3-(methoxymethoxy)naphthalene 

Relevant articles and documents

Kras-G12C inhibitor heterocyclic compounds

The invention relates to Kras-G12C inhibitor heterocyclic compounds represented by formula I, a preparation method thereof, and application of the Kras-G12C inhibitor heterocyclic compounds in prevention and treatment of tumor diseases such as lung cancer, colorectal cancer and pancreatic cancer. In the preparation process, the compounds of the general formula I are obtained through a series of reactions such as SN2 reaction, protection, coupling reaction, deprotection, condensation reaction and the like.

KRAS G12C INHIBITORS

The present invention relates to compounds that, inhibit KRas G12C, In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE

The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.