78137-76-5

Usage

Chemical Properties

brown solid

InChI:InChI=1/C6H4BrNO3/c7-5-2-1-4(9)3-6(5)8(10)11/h1-3,9H

Synthetic route

meta-nitrophenol (554-84-7) → 4-bromo-3-nitrophenol (78137-76-5)

Conditions	Yield
With 1-butyl-3-methylpyridinium tribromide at 20℃;	98%
With 1,3-di-n-butyl-1H-imidazol-3-ium tribromide at 20℃; for 0.133333h; Neat (no solvent); regioselective reaction;	95%
With 1,2-ethanediylbis(triphenylphosphonium) ditribromide In methanol; dichloromethane at 20℃; for 0.0833333h; Solvent; regioselective reaction;	85%
at 120 - 140℃; Einleiten von mit CO2 verduenntem Brom-Dampf;
With hydrogenchloride; carbon dioxide; bromine

4-bromo-3-nitroanizole (5344-78-5) → 4-bromo-3-nitrophenol (78137-76-5)

Conditions	Yield
Stage #1: 4-bromo-3-nitroanizole With boron tribromide In dichloromethane at -78 - 20℃; for 31h; Stage #2: With water In dichloromethane at 0℃;	87%
Stage #1: 4-bromo-3-nitroanizole With boron tribromide In dichloromethane at -78 - 20℃; for 31h; Stage #2: With water In dichloromethane at 0℃;	87%
With boron tribromide In dichloromethane at -78 - 20℃;	83%

4-hydroxy-2-nitroaniline (610-81-1) → 4-bromo-3-nitrophenol (78137-76-5)

Conditions	Yield
With hydrogen bromide Diazotization.Behandlung der Diazoniumsalz-Loesung mit Kupfer-Pulver und wss. HBr;
With sulfuric acid Diazotization.man versetzt mit einer konz. Kaliumbromidloesung und fuegt Kupferpulver hinzu;
Stage #1: 4-hydroxy-2-nitroaniline With hydrogen bromide; sodium nitrite In water at 0 - 10℃; for 1h; Stage #2: With hydrogen bromide; copper(I) bromide at 40 - 45℃; for 1h;	13.1 g

meta-nitrophenol (554-84-7) + bromine (7726-95-6) → 4-bromo-3-nitrophenol (78137-76-5)

Conditions	Yield
at 120 - 140℃;

4-acetamido-3-nitrophenyl acetate (2243-69-8) → 4-bromo-3-nitrophenol (78137-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous hydrobromic acid 2: aqueous HBr / Diazotization.Behandlung der Diazoniumsalz-Loesung mit Kupfer-Pulver und wss. HBr View Scheme

3-nitro-aniline (99-09-2) → 4-bromo-3-nitrophenol (78137-76-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: Diazotization 2: 120 - 140 °C / Einleiten von mit CO2 verduenntem Brom-Dampf View Scheme

4-bromo-3-nitrophenol (78137-76-5) + p-methoxybenzyl chloride (824-94-2) → C14H12BrNO4

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 3h; Inert atmosphere;	100%

4-bromo-3-nitrophenol (78137-76-5) + vinyl zinc chloride (78389-90-9) → 3-nitro-4-vinylphenol

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0) In tetrahydrofuran at 100℃; for 2h;	100%

tetravinylsilane (1112-55-6) + 4-bromo-3-nitrophenol (78137-76-5) → 3-nitro-4-vinylphenol

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0) In tetrahydrofuran at 80℃; for 2h;	100%

4-bromo-3-nitrophenol (78137-76-5) + tri-n-butyl(vinyl)tin (7486-35-3) → 3-nitro-4-vinylphenol

Conditions	Yield
Stage #1: 4-bromo-3-nitrophenol; tri-n-butyl(vinyl)tin With tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 80℃; for 4h; Stage #2: With potassium fluoride In 1,4-dioxane at 20℃; for 2h;	100%

4-bromo-3-nitrophenol (78137-76-5) + tert-butyldimethylsilyl chloride (18162-48-6) → (4-bromo-3-nitro)phenoxy-tert-butyl-dimethyl-silane

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 3.5h;	99%

4-bromo-3-nitrophenol (78137-76-5) + benzyl bromide (100-39-0) → 2-Bromo-5-benzyloxy-nitrobenzene (4514-28-7)

Conditions	Yield
With potassium carbonate In acetone; acetonitrile for 17h; Heating;	95%
With potassium carbonate In acetone	91%
With potassium carbonate In acetone; acetonitrile for 17h; Heating / reflux;	78%

triisopropylsilyl chloride (13154-24-0) + 4-bromo-3-nitrophenol (78137-76-5) → (4-bromo-3-nitrophenoxy)(triisopropyl)silane (1380316-20-0)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 18℃; for 20h;	95%

4-bromo-3-nitrophenol (78137-76-5) + 1-Chloro-4-(chloromethyl)benzene (104-83-6) → C13H9BrClNO3

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 3h; Inert atmosphere;	94.8%

4-bromo-3-nitrophenol (78137-76-5) + 2-(bromomethyl)naphthalene (3163-27-7) → 2-Bromo-5-(1-naphthalenylmethoxy)-nitrobenzene

Conditions	Yield
With potassium carbonate In N-methyl-acetamide	92%

4-bromo-3-nitrophenol (78137-76-5) + (4-bromomethyl)-phenoxy-allyl acetate → [4-(4-Bromo-3-nitro-phenoxymethyl)-phenoxy]-acetic acid allyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 22℃; for 3h;	91%

trifluoromethylsulfonic anhydride (358-23-6) + 4-bromo-3-nitrophenol (78137-76-5) → 4-bromo-3-nitrophenyl trifluoromethanesulfonate

Conditions	Yield
With pyridine In dichloromethane at 0 - 30℃; for 0.5h; Inert atmosphere;	90%

4-bromo-3-nitrophenol (78137-76-5) + (4-tert-butoxycarbonylaminophenyl)boronic acid pinacol ester (330793-01-6) → tert-butyl (4'-hydroxy-2'-nitro-[1,1'-biphenyl]-4-yl)carbamate

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane at 110℃; for 12h;	72%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane at 110℃; for 12h; Reflux;	72%

4-bromo-3-nitrophenol (78137-76-5) → 3-amino-4-bromophenol (100367-37-1)

Conditions	Yield
With iron(III) oxide; hydrazine hydrate In ethanol for 1.5h; Reflux;	70.9%

(1,3-thiazol-2-yl)methanol (14542-12-2) + 4-bromo-3-nitrophenol (78137-76-5) → 2-((4-bromo-3-nitrophenoxy)methyl)thiazole

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In toluene at 0℃; Mitsunobu Displacement; Inert atmosphere; Reflux;	69%

Trimethyl borate (121-43-7) + 4-bromo-3-nitrophenol (78137-76-5) → C6H6BNO5

Conditions	Yield
Stage #1: 4-bromo-3-nitrophenol With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: Trimethyl borate In tetrahydrofuran at 20℃; for 1h; Stage #3: With hydrogenchloride In tetrahydrofuran for 1h;	53%

1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1Hpyrrole-2-carbonitrile + 4-bromo-3-nitrophenol (78137-76-5) → 5-(4-hydroxy-2-nitrophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

Conditions	Yield
With palladium diacetate; cesium fluoride; catacxium A In 1,4-dioxane; water at 80℃; for 1h; Suzuki Coupling; Inert atmosphere; Sealed tube;	30%

4-bromo-3-nitrophenol (78137-76-5) + chloroacetone (78-95-5) → 1-(4-Bromo-3-nitro-phenoxy)-propan-2-one (78137-77-6)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide

4-bromo-3-nitrophenol (78137-76-5) + benzyl chloride (100-44-7) → 2-Bromo-5-benzyloxy-nitrobenzene (4514-28-7)

Conditions	Yield
With potassium hydroxide

4-bromo-3-nitrophenol (78137-76-5) → [4-(tert-butyl-dimethyl-silanyloxy)-2-nitro-phenyl]-(2'-nitrophenyl)-amine

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / Et3N / CH2Cl2 / 3.5 h / 20 °C 2: 70 percent / rac-BINAP; Cs2CO3 / Pd2(dba)3 / toluene / 0.5 h / 160 °C / microwave irradiation View Scheme

4-bromo-3-nitrophenol (78137-76-5) → [4-(3-Amino-4-bromo-phenoxymethyl)-phenoxy]-acetic acid allyl ester (1026914-86-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / K2CO3 / dimethylformamide / 3 h / 22 °C 2: 64 percent / Na2S2O4 / tetrahydrofuran; H2O / 4 h / 22 °C View Scheme

4-bromo-3-nitrophenol (78137-76-5) → 4-Oxo-5,6,9,10-tetradehydro-4,5-secofuranoeremophilan-5,1-carbolacton (53820-33-0)

Conditions	Yield
Multi-step reaction with 7 steps 1: K2CO3, KI / dimethylformamide 2: 82 percent / TiCl3 / ethanol 3: 1.)NO(1+) / 1.) diazotation 4: AlH(C4H9)2 / toluene 5: 27 percent / Li / tetrahydrofuran 6: 10 percent / lithium butyl / -100 °C 7: 84 percent / hydrolysis View Scheme

4-bromo-3-nitrophenol (78137-76-5) → 6-amino-5-brom-3-methylbenzofuran (78137-78-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3, KI / dimethylformamide 2: 82 percent / TiCl3 / ethanol View Scheme

4-bromo-3-nitrophenol (78137-76-5) → 5-Bromo-3-methyl-benzofuran-6-carbonitrile (78137-79-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3, KI / dimethylformamide 2: 82 percent / TiCl3 / ethanol 3: 1.)NO(1+) / 1.) diazotation View Scheme

4-bromo-3-nitrophenol (78137-76-5) → 5-Bromo-3-methyl-benzofuran-6-carbaldehyde (78137-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3, KI / dimethylformamide 2: 82 percent / TiCl3 / ethanol 3: 1.)NO(1+) / 1.) diazotation 4: AlH(C4H9)2 / toluene View Scheme

4-bromo-3-nitrophenol (78137-76-5) → 1-(5-Bromo-3-methyl-benzofuran-6-yl)-3-(2-methyl-[1,3]dioxolan-2-yl)-propan-1-ol (78137-81-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: K2CO3, KI / dimethylformamide 2: 82 percent / TiCl3 / ethanol 3: 1.)NO(1+) / 1.) diazotation 4: AlH(C4H9)2 / toluene 5: 27 percent / Li / tetrahydrofuran View Scheme

Upstream product

• 554-84-7 meta-nitrophenol 
• 610-81-1 4-hydroxy-2-nitroaniline 
• 5344-78-5 4-bromo-3-nitroanizole 
• 99-09-2 3-nitro-aniline 
• 2243-69-8 4-acetamido-3-nitrophenyl acetate 
• 7726-95-6 bromine 

Downstream Products

• 78137-77-6 1-(4-Bromo-3-nitro-phenoxy)-propan-2-one 
• 4514-28-7 2-Bromo-5-benzyloxy-nitrobenzene 
• 344780-50-3 2-bromo-5-pivaloyloxynitrobenzene 
• 1313530-04-9 C₁₈H₁₇NO₃ 
• 1313530-07-2 C₁₉H₁₆N₂O₃ 
• 372094-05-8 6-hydroxy-2-methyl-3-phenyl-1H-indole 
• 139085-95-3 1-bromo-4-ethoxy-2-nitrobenzene 
• 129722-12-9 aripiprazole 

Relevant academic research and scientific papers

3 - Amino - 4 - bromophenol synthetic method

The invention relates to a method for synthesizing 3-amino-4-bromophenol. The method comprises the following steps of: (1) diazotization reaction: dissolving 3-nitro-4-aminophenol used as a raw material into hydrobromic acid, and dropping a sodium nitrite aqueous solution at 0-10 DEG C for reacting for 1-3 hours to obtain a 3-nitrophenol-4-diazonium brine solution; (2) bromination reaction: dropping the solution obtained in the step (1) into a hydrobromic acid aqueous solution of cuprous bromide, stirring at 40-50 DEG C for reacting, and crystallizing and filtering to obtain a 3-nitro-4-bromophenol solid; and (3) reduction reaction: dissolving the solid obtained in the step (2) into alcohol, adding an iron oxide catalyst, heating up to 50-100 DEG C, and adding a hydrazine hydrate aqueous solution to the mixture for reacting for 2-5 hours to obtain the 3-amino-4-bromophenol. The synthesis method of the 3-amino-4-bromophenol has the advantages of reasonable design, moderate condition, easiness of operation and higher product yield and is suitable for industrial production.

The synthesis of 1,2-ethanediylbis(triphenylphosphonium) ditribromide as a new brominating agent in the presence of solvents and under solvent-free conditions

Abstract: 1,2-Ethanediylbis(triphenylphosphonium) ditribromide was quantitatively prepared and used for the bromination of anilines and phenols in the presence of a mixed solvent system (DCM/MeOH 2:1) and also under solvent-free conditions. This new ionic liquid has advantages over similar brominating agents in terms of short reaction time, simple workup, regioselectivity and high yields. Single-crystal X-ray analysis of title salt revealed that the bistriphenylphosphonium cation is organized around an inversion center located at the center of the –CH2–CH2– bridge and the two triphenylphosphine segments are anti with respect to one another. All the tribromide anions adopt a linear geometry with different Br–Br–Br bond angles for each anion. Graphical Abstract: [Figure not available: see fulltext.]

PRIMARY CARBOXAMIDES AS BTK INHIBITORS

The invention provides carboxamide compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions, including rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, Crohn's disease, inflammatory bowel disease, ulcerative colitis, psoriatic arthritis, psoriasis, ankylosing spondylitis, interstitial cystitis, asthma, systemic lupus erythematosus, lupus nephritis, B cell chronic lymphocytic lymphoma, multiple sclerosis, chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, B-cell non-Hodgkin's lymphoma, activated B-celllike diffuse large B-cell, lymphoma, multiple myeloma, diffuse large B-celllymphoma, follicular lymphoma, hairy cell leukemia or Lymphoblastic lymphoma.

KAT II INHIBITORS

The present invention relates to compounds 3-amino-1-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonitrile, 3-amino-1-hydxoxy-7-(2-methoxyethoxy)-3,4-dihydro-quinolin-2(1H)-one, and 3-amino-1-hydroxy-7-[(1S)-2-methoxy-1-methylethoxy]-3,4-dihydroquinolin-2(1H)-one, including racemic mixtures and resolved enantiomers thereof, to pharmaceutically acceptable salts thereof, and to the treatment of cognitive deficits associated with schizophrenia and other psychiatric, neurodegenerative and/or neurological disorders in mammals, including humans

Rapid synthesis of diversely functionalized 3,4,7-trisubstituted indoles

Synthetic approaches are described for the synthesis of 4-alkoxyindole-7-carboxamides and 4-alkoxy-3-cyanoindole-7-carboxamides, which are useful intermediates in medicinal chemistry research. Two strategies were employed, highlighted by a Bartoli indole synthesis or a sequential and regioselective use of chlorosulfonyl isocyanate to install both the 3-cyano and 7-carboxamido groups. These routes are scalable and afford diversely functionalized indoles for further elaboration.

Mild, efficient, and regioselective monobromination of arylamines and phenols using [BBIm]Br3 as a new reagent

We report here an efficient method for the synthesis and characterization of the room-temperature ionic liquid 1,3-di-n-butylimidazolium tribromide ([BBIm]Br3) (2) and its application as an efficient reagent and solvent for regioselective bromination of arylamines and phenols under mild conditions. The bromination was carried out in the absence of organic solvents, and in most cases, the only extraction solvent needed was water. The spent 1,3-di-n-butylimidazolium bromide (1) was easily recycled.

An efficient, rapid, and regioselective bromination of anilines and phenols with 1-butyl-3-methylpyridinium tribromide as a new reagent/solvent under mild conditions

1-Butyl-3-methylpyridinium tribromide, [BMPy]Br3 proves to be a highly efficient, regioselective reagent/solvent for nuclear bromination of various anilines and phenols. The synthesis and characterization of the room temperature ionic liquid [BMPy]Br3 (2) is described. The bromination was carried out in the absence of organic solvents and in most cases the only extraction solvent needed was water. The spent 1-butyl-3-methylpyridinium bromide (1) was easily recycled.

Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof

The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (e.g., indazoles and benzothiazoles), which act as ligands for the α7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

1 H-INDAZOLES, BENZOTHIAZOLES, 1,2-BENZOISOXAZOLES, 1,2-BENZOISOTHIAZOLES, AND CHROMONES AND PREPARATION AND USES THEREOF

The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nAChR), activation of nAChRs, and the treatment of -disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (indazoles and benzothiazoles), which act as ligands for the α7 nAChR subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

2,3-Dimethoxybenzo[i]phenanthridines: Topoisomerase I-targeting anticancer agents

Appropriately substituted benzo[i]phenanthridines structurally related to nitidine, a benzo[c]phenanthridine alkaloid with antitumor activity, are active as topoisomerase I-targeting agents. Studies on benzo[i]phenanthridines have indicated analogues that possess a 2,3-methylenedioxy moiety and at least one and preferably two methoxyl groups at the 8- and 9-positions, such as 8,9-dimethoxy-2,3-methylenedioxybenzo[i]phenanthridine, 2, are active as topoisomerase I-targeting agents. Tetramethoxylated benzo[i]phenanthridines, wherein the 2,3-methylenedioxy moiety is replaced with methoxyl groups at the 2- and 3-position, are inactive as a topoisomerase I-targeting agent. These results initially suggested that the 2,3-methylenedioxy moiety was critical to the retention of potent activity. Further studies revealed that 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine, 7a, is more potent than 2 as a topoisomerase I-targeting agent. The observation that 2,3-dimethoxylated benzo[i]phenanthridines can actually exhibit enhanced activity prompted the present study in which several 8-substituted 2,3-dimethoxybenzo[i]phenanthridines were prepared and their pharmacological activities evaluated. The influence of NH2, CN, CH2OH, OBn, OCH3, OH, and NHCOCH3substituents at the 8-position on the relative activity of these 2,3-dimethoxybenzo[i]phenanthridines was examined. Relative to these derivatives, 7a was the most potent topoisomerase I-targeting agent, possessing similar cytotoxicity to that of nitidine in the human lymphoblast tumor cell line, RPMI8402.