3970-37-4

Basic information

• Product Name: 1-BROMO-2-CHLORO-3-NITROBENZENE
• Synonyms: 1-BROMO-2-CHLORO-3-NITROBENZENE
• CAS NO: 3970-37-4
• Molecular Formula: C₆H₃BrClNO₂
• Molecular Weight: 236.45
• Mol File: 3970-37-4.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 290.355 °C at 760 mmHg
• Flash Point: 129.403 °C
• Appearance: /
• Density: 1.827 g/cm³
• Vapor Pressure: 0.004mmHg at 25°C
• Refractive Index: 1.619
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 1-BROMO-2-CHLORO-3-NITROBENZENE(CAS DataBase Reference)
• NIST Chemistry Reference: 1-BROMO-2-CHLORO-3-NITROBENZENE(3970-37-4)
• EPA Substance Registry System: 1-BROMO-2-CHLORO-3-NITROBENZENE(3970-37-4)

Safety Data

• Hazardous Substances Data: 3970-37-4(Hazardous Substances Data)

Usage

Uses

1-Bromo-2-chloro-3-nitrobenzene is a reagent used in pharmaceutical synthesis. Used in the synthesis of benzodiazepinone bromodomain inhibitor CPI-?637 which may be applicable to cancer therapies.

InChI:InChI=1/C6H3BrClNO2/c7-4-2-1-3-5(6(4)8)9(10)11/h1-3H

Synthetic route

2-chloro-3-nitrobezoic acid (3970-35-2) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
With bromine; mercury(II) oxide In tetrachloromethane for 3.5h; Heating; Irradiation;	96%
With bromine; mercury(II) oxide In tetrachloromethane light;	96%
With bromine; mercury(II) oxide In tetrachloromethane at 20℃; for 4.5h; Heating / reflux; Irradiation;	95%

2-bromo-6-nitroaniline (59255-95-7) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
With tert.-butylnitrite; copper dichloride In acetonitrile at 60℃; for 1h; Inert atmosphere;	86.2%
With tert.-butylnitrite; copper dichloride In acetonitrile at 60℃; for 1h; Inert atmosphere;	82.7%
Diazotization.Eintropfen der Diazoniumloesung in Kupferchloruerloesung;
Stage #1: 2-bromo-6-nitroaniline With sodium nitrate; sulfuric acid; acetic acid at 25 - 35℃; for 0.5h; Stage #2: With hydrogenchloride; copper(l) chloride In water at 70℃;

2-chloro-3-nitroaniline (3970-41-0) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
Stage #1: 2-chloro-3-nitroaniline With hydrogen bromide; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #2: With hydrogen bromide; copper(I) bromide In water at 70℃; for 1h; Sandmeyer Reaction;	71%
With tert.-butylnitrite; copper(ll) bromide In acetonitrile at 65℃; for 0.5h;

1,2-dibromo-3-nitrobenzene (26429-41-4) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
With tetrabutylammonium bromchlorocuprate(I) In chlorobenzene at 90℃; Rate constant; halogen exchange reaction of 3-bromo-2-iodonitrobenzene with tetrabutylammonium bromochlorocuprate(I), NMR study;
With tetrabutylammonium dichlorocuprate(I) In dimethyl sulfoxide at 85℃; Rate constant; Thermodynamic data; Kinetics; solvent dependence, ΔH(excit), ΔS(excit);
Multi-step reaction with 2 steps 1: alcohol; ammonia / 180 °C 2: Diazotization.Eintropfen der Diazoniumloesung in Kupferchloruerloesung View Scheme

1-bromo-2-iodo- 3-nitrobenzene (32337-96-5) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
With tetrabutylammonium bromchlorocuprate(I) In chlorobenzene at 90℃; Rate constant; halogen exchange reaction of 3-bromo-2-iodonitrobenzene with tetrabutylammonium bromochlorocuprate(I), NMR study;

1,2-dibromobenzene (583-53-9) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: nitric acid 2: alcohol; ammonia / 180 °C 3: Diazotization.Eintropfen der Diazoniumloesung in Kupferchloruerloesung View Scheme
Multi-step reaction with 3 steps 1: nitric acid 2: alcohol; ammonia / 180 °C 3: Diazotization.Eintropfen der Diazoniumloesung in Kupferchloruerloesung View Scheme

Ar + mercury(II) oxide (21908-53-2) + 2-chloro-3-nitrobezoic acid (3970-35-2) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
With bromine In tetrachloromethane

2-fluoro-3-bromonitrobenzene (58534-94-4) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / methanol / 16 h / 100 °C / Sealed tube 2: tert.-butylnitrite; copper dichloride / acetonitrile / 1 h / 60 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: ammonia / methanol / 16 h / 100 °C / Sealed tube 2: tert.-butylnitrite; copper dichloride / acetonitrile / 1 h / 60 °C / Inert atmosphere View Scheme

3-nitro-aniline (99-09-2) → 1-bromo-2-chloro-3-nitrobenzene (3970-37-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-chloro-succinimide / N,N-dimethyl-formamide / 1 h / 20 - 75 °C 2.1: hydrogen bromide; sodium nitrite / water / 0.5 h / 0 - 5 °C 2.2: 1 h / 70 °C View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 3-bromo-2-chlorobenzenamine (56131-46-5)

Conditions	Yield
With iron; acetic acid In ethanol; water at 20℃; for 16h;	100%
With iron; ammonium chloride In ethanol; water at 60℃; for 4h;	93.88%
With iron; ammonium chloride In ethanol; water at 60℃; for 4h;	93.88%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + tert-butylamine (75-64-9) → 2-bromo-N-tert-butyl-6-nitroaniline (183801-89-0)

Conditions	Yield
In ethanol at 150℃; for 96h;	93%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + methylamine (74-89-5) → 2-bromo-N-methyl-6-nitro-aniline (1004618-77-2)

Conditions	Yield
In methanol; ethanol at 85℃; for 2h;	92%

(R)-3-aminobutanoic acid (3775-73-3) + 1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → (R)-3-((2-bromo-6-nitrophenyl)amino)butanoic acid

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃;	90%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + phenylmethanethiol (100-53-8) → benzyl(2-bromo-6-nitrophenyl)sulfane

Conditions	Yield
With sodium In ethanol for 1.08333h; Reflux;	88.5%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 2-fluoro-3-bromonitrobenzene (58534-94-4)

Conditions	Yield
With potassium fluoride; cesium fluoride In N,N-dimethyl-formamide	73%
With potassium fluoride In N,N-dimethyl-formamide at 150℃;
With potassium fluoride; cesium fluoride In DMF (N,N-dimethyl-formamide) for 5h; Heating / reflux;

9-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-9H-carbazole (785051-54-9) + 1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → C24H15ClN2O2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene at 80℃; for 6h;	70%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + (2-(9H-carbazol-9-yl)phenyl)boronic acid (1189047-28-6) → C24H15ClN2O2

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 120℃; for 3h; Suzuki Coupling;	66%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 120℃; for 3h;	66%

morpholine (110-91-8) + 1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 4-(2-chloro-3-nitrophenyl)morpholine (1146413-10-6)

Conditions	Yield
With caesium carbonate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran at 20 - 85℃; for 16.5h;	58.4%
With palladium diacetate; caesium carbonate In tetrahydrofuran at 85℃; for 16h; Inert atmosphere;	49.5%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + sodium methylate (124-41-4) → 2-bromo-6-nitrophenyl methyl ether (98775-19-0)

Conditions	Yield
With methanol at 100℃; for 3h; Autoclave;	58%
In methanol

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + vinyl magnesium bromide (1826-67-1) → 6-bromo-7-chloro-1H-indole

Conditions	Yield
In tetrahydrofuran at -78℃; for 3h;	49%
In tetrahydrofuran at -40℃; for 1h; Inert atmosphere;	32%
In tetrahydrofuran at -78℃; for 3h;	32%
In tetrahydrofuran at -40℃; for 1h;

pyrrolidine (123-75-1) + 1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → C10H11ClN2O2

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran at 85℃; for 18h;	39.64%

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + (phenylthio)acetonitrile (5219-61-4) → (2-Bromo-3-chloro-4-nitro-phenyl)-acetonitrile (1176315-49-3)

Conditions	Yield
With sodium hydroxide In dimethyl sulfoxide at 18.5 - 22℃;	19%

piperidine (110-89-4) + 1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 1-(2-Bromo-6-nitro-phenyl)-piperidine (98775-21-4)

Conditions	Yield
Heating;

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) + 3-pyridylboronic acid (1692-25-7) → 3-(2-chloro-3-nitro-phenyl)-pyridine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 12h; Arylation; Heating;

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 2-chloro-3-(3-pyridyl)aniline (264617-06-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine)palladium(0); Na2CO3 / 1,2-dimethoxy-ethane; H2O / 12 h / Heating 2: stannous chloride; aq. HCl View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → (2-chloro-3-pyridin-3-yl-phenyl)-carbamic acid phenyl ester (264617-22-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine)palladium(0); Na2CO3 / 1,2-dimethoxy-ethane; H2O / 12 h / Heating 2: stannous chloride; aq. HCl 3: 100 percent / Et3N / CH2Cl2 / 18 h / 20 °C View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 5-methoxy-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid (2-chloro-3-pyridin-3-yl-phenyl)-amide

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrakis(triphenylphosphine)palladium(0); Na2CO3 / 1,2-dimethoxy-ethane; H2O / 12 h / Heating 2: stannous chloride; aq. HCl 3: 100 percent / Et3N / CH2Cl2 / 18 h / 20 °C 4: 45 percent / Et3N / dimethylformamide / 1 h / 95 - 105 °C View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 3-Bromo-N2-tert-butyl-benzene-1,2-diamine (183802-24-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 5-bromo-1,2,3,4-tetrahydroquinoxalin-2-one (183801-94-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature 3: 77 percent / diisopropylethylamine / tetrahydrofuran / a) -60 deg C, 3 h, b) RT, 16 h 4: 79 percent / diisopropylethylamine, NaI / acetonitrile / 22 h / Heating 5: 1.) TFA, 2.) NaBH4 / 1.) RT, 20 h, 2.) MeOH, EtOH, RT, 6 h View Scheme
Multi-step reaction with 5 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature 3: 77 percent / diisopropylethylamine / tetrahydrofuran / a) -60 deg C, 3 h, b) RT, 16 h 4: 79 percent / diisopropylethylamine, NaI / acetonitrile / 22 h / Heating 5: TFA / 20 h / Ambient temperature View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 5-Bromo-1H-quinoxalin-2-one

Conditions	Yield
Multi-step reaction with 5 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature 3: 77 percent / diisopropylethylamine / tetrahydrofuran / a) -60 deg C, 3 h, b) RT, 16 h 4: 79 percent / diisopropylethylamine, NaI / acetonitrile / 22 h / Heating 5: TFA / 20 h / Ambient temperature View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 5-bromo-4-tert-butyl-1,2,3,4-tetrahydroquinoxalin-2-one (183801-92-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature 3: 77 percent / diisopropylethylamine / tetrahydrofuran / a) -60 deg C, 3 h, b) RT, 16 h 4: 79 percent / diisopropylethylamine, NaI / acetonitrile / 22 h / Heating View Scheme

1-bromo-2-chloro-3-nitrobenzene (3970-37-4) → 6,7-Dihydro-1H-pyrido[1,2,3-de]quinoxaline-2,5-dione (180990-30-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature 3: 77 percent / diisopropylethylamine / tetrahydrofuran / a) -60 deg C, 3 h, b) RT, 16 h 4: 79 percent / diisopropylethylamine, NaI / acetonitrile / 22 h / Heating 5: 1.) TFA, 2.) NaBH4 / 1.) RT, 20 h, 2.) MeOH, EtOH, RT, 6 h 6: 63 percent / Et3N, Pd(PPh3)4 / dimethylformamide / 6 h / 120 °C 7: 79 percent / H2, p-TsOH*H2O / 5percent Pd/C / ethanol; methanol / 40 h / 2068.6 Torr / Ambient temperature View Scheme
Multi-step reaction with 7 steps 1: 93 percent / ethanol / 96 h / 150 °C 2: 97 percent / aq. TiCl3, aq. AcONa / methanol / 2 h / Ambient temperature 3: 77 percent / diisopropylethylamine / tetrahydrofuran / a) -60 deg C, 3 h, b) RT, 16 h 4: 79 percent / diisopropylethylamine, NaI / acetonitrile / 22 h / Heating 5: TFA / 20 h / Ambient temperature 6: 63 percent / Et3N, Pd(PPh3)4 / dimethylformamide / 6 h / 120 °C 7: 79 percent / H2, p-TsOH*H2O / 5percent Pd/C / ethanol; methanol / 40 h / 2068.6 Torr / Ambient temperature View Scheme

Upstream product

• 121-18-6 3-nitro-4-chlorobenzenesulfonic acid 
• 99-09-2 3-nitro-aniline 
• 58534-94-4 2-fluoro-3-bromonitrobenzene 
• 21908-53-2 mercury(II) oxide 
• 3970-35-2 2-chloro-3-nitrobezoic acid 
• 583-53-9 2,3-dibromobenzene 
• 3970-41-0 2-chloro-3-nitroaniline 
• 32337-96-5 1-bromo-2-iodo-3-nitro-benzene 
• 26429-41-4 1,2-dibromo-3-nitrobenzene 
• 59255-95-7 2-bromo-6-nitroaniline 

Downstream Products

• 98775-19-0 2-bromo-6-nitrophenyl methyl ether 
• 183801-89-0 2-bromo-N-tert-butyl-6-nitroaniline 
• 56131-46-5 3-bromo-2-chlorobenzenamine 
• 1269233-02-4 N-(3-bromo-2-chlorophenyl)propane-1-sulfonamide 
• 1884712-47-3 CPI-637 
• 58534-94-4 2-fluoro-3-bromonitrobenzene 

Relevant articles and documents

Preparation method 2 - chloro -3 - bromoaniline

The invention discloses a preparation method of 2 - chloro -3 - bromoaniline, and the specific steps of the preparation method are as follows: (1) the compound II and the bromosuccinimide are subjected to electrophilic substitution reaction to generate the compound III. (2) The sulfonic acid group of the compound III was removed to give compound IV. (3) Compound IV is reduced to compound I with a safety powder, i.e. said 2 - chloro -3 - bromoaniline. To the invention, 4 - chlorine -3 - nitrobenzene sulfonic acid is used as a starting raw material in a full synthetic route process, reagents with large toxicity and large pollution are avoided, and meanwhile, the raw materials are low in price and higher in yield.

SUBSTITUTED QUINAZOLINE COMPOUNDS AND THEIR USE AS INHIBITORS OF G12C MUTANT KRAS, HRAS AND/OR NRAS PROTEINS

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R, R1, R2a, R2b, R2c, A, B, L1 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Compounds and Compositions as Protein Kinase Inhibitors

The present invention provides compounds of Formula I or II: wherein R1, R1b, R2, R3, R4, R5, R6 and R7 are defined herein. The compounds of Formula (I) or (II) and pharmaceutical compositions thereof are useful for the treatment of B-Raf-associated diseases.