450-88-4

Basic information

• Product Name: 2-Bromo-5-fluoroanisole
• Synonyms: BUTTPARK 87\07-62;2-BROMO-5-FLUOROANISOLE;1-Bromo-4-fluoro-2-methoxybenzene;2-Bromo-5-fluoroanisole98+%;1-Bromo-4-fluoro-2-methoxybenzene, 2-Bromo-5-fluorophenyl methyl ether;2-BroMo-5-fluoroanisole, 95.0%(GC)
• CAS NO: 450-88-4
• Molecular Formula: C₇H₆BrFO
• Molecular Weight: 205.02
• Product Categories: Anisole
• Mol File: 450-88-4.mol
• Article Data: 33

Chemical Properties

• Boiling Point: 143-145 °C
• Flash Point: 90 °C
• Appearance: /
• Density: 1.5983
• Vapor Pressure: 0.849mmHg at 25°C
• Refractive Index: 1.542
• Storage Temp.: Room temperature.
• CAS DataBase Reference: 2-Bromo-5-fluoroanisole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-5-fluoroanisole(450-88-4)
• EPA Substance Registry System: 2-Bromo-5-fluoroanisole(450-88-4)

Safety Data

• Hazard Codes: Xn
• Statements: 36/37/38-36-22
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• Hazardous Substances Data: 450-88-4(Hazardous Substances Data)

Usage

Chemical Properties

Colorless liquid to pale yellow liquid

InChI:InChI=1/C7H6BrFO/c1-10-7-4-5(9)2-3-6(7)8/h2-4H,1H3

Synthetic route

dimethyl sulfate (77-78-1) + 2-bromo-5-fluorophenol (147460-41-1) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
With potassium carbonate In acetone at 60℃; for 2h;	100%
With potassium carbonate In acetone at 60℃; for 2h;	100%
With potassium carbonate In acetone at 60℃; for 2h;	100%

4-fluoro-2-methoxyaniline (450-91-9) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
Stage #1: 4-fluoro-2-methoxyaniline With sodium nitrite In water at -5 - 0℃; Stage #2: With hydrogen bromide; copper(I) bromide In water at 105℃;	93%
Diazotization;

2-bromo-5-fluorophenol (147460-41-1) + methyl iodide (74-88-4) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;	93%
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 3h;
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 3h;

2,4-difluorobromobenzene (348-57-2) + potassium methanolate (865-33-8) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
In tetrahydrofuran at 65 - 68℃; for 5h;	93%
In tetrahydrofuran at 65 - 68℃; for 5h;	93%
In tetrahydrofuran at 65℃; for 4h;	90%

4-fluoro-2-methoxy-benzoic acid (395-82-4) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
With potassium phosphate; tetrabuthylammonium tribromide In acetonitrile at 100℃; for 16h;	75%

methanol (67-56-1) + 2,4-difluorobromobenzene (348-57-2) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
Stage #1: methanol With sodium hydride In tetrahydrofuran at 0℃; for 15h; Stage #2: 2,4-difluorobromobenzene In tetrahydrofuran at 20℃; for 17h; Further stages.;	42%

2,4-difluorobromobenzene (348-57-2) + potassium methanolate (865-33-8) → 1-Bromo-2,4-dimethoxybenzene (17715-69-4) + 1-bromo-2-fluoro-4-methoxybenzene (458-50-4) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
In tetrahydrofuran at 65 - 68℃; for 22h; Inert atmosphere; regioselective reaction;	A 9% B n/a C n/a

1-fluoro-3-methoxybenzene (456-49-5) → 1-bromo-2-fluoro-4-methoxybenzene (458-50-4) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
With bromine; tetramethylammonium bromide In liquid sulphur dioxide at -23℃; Product distribution; Rate constant;
With bromine; iron In chloroform at -60℃; for 2h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

N-Formylpiperidine (2591-86-8) + 1-fluoro-3-methoxybenzene (456-49-5) → 2-fluoro-4-methoxy-benzaldehyde (331-64-6) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + 2-methoxy-4-fluorobenzaldehyde (450-83-9)

Conditions	Yield
Yield given. Multistep reaction;

4-fluoro-2-methoxy-1-nitrobenzene (448-19-1) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: iron; aqueous acetic acid 2: Diazotization View Scheme
Multi-step reaction with 2 steps 1.1: 5%-palladium/activated carbon; hydrogen / ethyl acetate / 30 - 35 °C / 3750.38 - 7500.75 Torr / Autoclave; Inert atmosphere 2.1: sodium nitrite / water / -5 - 0 °C 2.2: 105 °C View Scheme

methanol (67-56-1) + 2,4-difluorobromobenzene (348-57-2) → 1-bromo-2-fluoro-4-methoxybenzene (458-50-4) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
With potassium tert-butylate In 1,4-dioxane at 20℃; Inert atmosphere; regioselective reaction;

2,4-difluorobromobenzene (348-57-2) + potassium methanolate (865-33-8) → 1-bromo-2-fluoro-4-methoxybenzene (458-50-4) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
With potassium tert-butylate In 1,4-dioxane at 20℃; for 24h; Inert atmosphere; regioselective reaction;

2,4-Difluoronitrobenzene (446-35-5) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydroxide / water; toluene / 55 - 60 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 60 - 100 °C 3.1: 5%-palladium/activated carbon; hydrogen / ethyl acetate / 30 - 35 °C / 3750.38 - 7500.75 Torr / Autoclave; Inert atmosphere 4.1: sodium nitrite / water / -5 - 0 °C 4.2: 105 °C View Scheme

5-fluoro-2-nitrophenol (446-36-6) → 1-bromo-4-fluoro-2-methoxybenzene (450-88-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 60 - 100 °C 2.1: 5%-palladium/activated carbon; hydrogen / ethyl acetate / 30 - 35 °C / 3750.38 - 7500.75 Torr / Autoclave; Inert atmosphere 3.1: sodium nitrite / water / -5 - 0 °C 3.2: 105 °C View Scheme

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + acetyl chloride (75-36-5) → 1-(5-bromo-2-fluoro-4-methoxyphenyl)ethan-1-one (914221-54-8)

Conditions	Yield
With aluminum (III) chloride In 1,2-dichloro-ethane at -10 - 5℃; for 1h;	100%
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With aluminum (III) chloride In 1,2-dichloro-ethane at -10 - 2℃; Stage #2: acetyl chloride In 1,2-dichloro-ethane at 0 - 5℃; for 1h;	100%
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With aluminum (III) chloride In dichloromethane at -5 - 20℃; Stage #2: acetyl chloride In dichloromethane at -5 - 0℃; for 6h;	89%
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene; acetyl chloride With aluminum (III) chloride In 1,2-dichloro-ethane at 0 - 10℃; for 1.16667h; Friedel-Crafts acylation; Inert atmosphere; Large scale reaction; Stage #2: With water In ethyl acetate; 1,2-dichloro-ethane at 0 - 20℃; Large scale reaction;	88%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + 4-fluoro-2-methoxyphenylboronic acid (179899-07-1) → 2,2'-dimethoxy-4,4'-difluorobiphenyl (5400-65-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water for 43h; Inert atmosphere; Reflux;	99%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + chloroacetone (78-95-5) → 1-[(5-fluoro-2-methoxyphenyl) thio]-2-propanone (476198-75-1)

Conditions	Yield
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With tert.-butyl lithium; sulfur In tetrahydrofuran; pentane at -78℃; for 0.25h; Stage #2: chloroacetone In tetrahydrofuran; pentane at -78℃; for 1h;	98%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + bis(pinacol)diborane (73183-34-3) → C13H17BBrFO3

Conditions	Yield
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Glovebox;	95%
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Glovebox;

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + bis(pinacol)diborane (73183-34-3) → C13H17BBrFO3

Conditions	Yield
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Glovebox;	95%

7-hydroxy-5,8-dimethyl-2-naphthonitrile + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 7-(4-fluoro-2-methoxyphenoxy)-5,8-dimethyl-2-naphthonitrile

Conditions	Yield
With copper(l) iodide; 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate In 1,4-dioxane Inert atmosphere; Sealed tube; Heating;	91%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → 4-(4-fluoro-2-methoxyphenyl)piperazine-1-carboxylic acid tert-butyl ester (1121600-04-1)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 16h; Temperature; Inert atmosphere;	90%
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene Inert atmosphere; Reflux;	58%
With palladium diacetate; sodium t-butanolate; XPhos In toluene at 90℃; Buchwald-Hartwig Coupling;

[1,2-13C2]-acetyl chloride (89186-79-8) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → [13C2]1-(5-bromo-2-fluoro-4-methoxyphenyl)ethanone

Conditions	Yield
With aluminum (III) chloride In dichloromethane	90%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + copper(I) cyanide (544-92-3) → 2-methoxy-4-fluorobenzonitrile (191014-55-8)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 180℃; for 5.5h;	85%
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene; copper(I) cyanide In 1-methyl-pyrrolidin-2-one at 180℃; for 5h; Stage #2: With ammonia In 1-methyl-pyrrolidin-2-one; water for 0.75h;
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene; copper(I) cyanide In 1-methyl-pyrrolidin-2-one at 180℃; for 5.5h; Stage #2: With ammonium hydroxide In 1-methyl-pyrrolidin-2-one; water at 20℃; for 0.75h;
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene; copper(I) cyanide In 1-methyl-pyrrolidin-2-one at 180℃; for 5.5h; Stage #2: With ammonia In 1-methyl-pyrrolidin-2-one; water at 20℃; for 0.75h;
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene; copper(I) cyanide In 1-methyl-pyrrolidin-2-one at 180℃; for 5.5h; Stage #2: With ammonia In 1-methyl-pyrrolidin-2-one; water at 20℃; for 0.75h;

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + 3-chloroprop-1-ene (107-05-1) → (2S,3S)-2-(4-fluoro-2-methoxyphenyl)-3-methyloxirane

Conditions	Yield
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With magnesium; lithium chloride In tetrahydrofuran at 70℃; for 1h; Stage #2: 3-chloroprop-1-ene With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 70℃; Stage #3: With Oxone; tetra(n-butyl)ammonium hydrogensulfate; potassium carbonate In water; acetonitrile at 0℃; for 1.5h;	85%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → C7H3(2)H3BrFO

Conditions	Yield
With water-d2; potassium carbonate; silver carbonate; cyclohexyldiphenylphosphine In toluene at 120℃; for 12h;	85%

4-(benzoyloxy)morpholine (5765-65-1) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → C11H14FNO2

Conditions	Yield
With norbornene; 1,4-bis(dicyclopentylphosphino)butane di-trifluoroborate; palladium diacetate; caesium carbonate; 1,7,7-trimethyl-endo-bicyclo[2.2.1]heptan-2-ol In 1,4-dioxane at 90℃; for 14h; Inert atmosphere; Sealed tube; chemoselective reaction;	83%

Trimethyl borate (121-43-7) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 4-fluoro-2-methoxyphenylboronic acid (179899-07-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran	82%

5-fluoro-7-hydroxy-8-methyl-2-naphthonitrile + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 5-fluoro-7-(4-fluoro-2-methoxyphenoxy)-8-methyl-2-naphthonitrile

Conditions	Yield
With copper(l) iodide; 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate In 1,4-dioxane Inert atmosphere; Sealed tube; Heating;	79%

5-chloro-7-hydroxy-8-methyl-2-naphthonitrile + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 5-chloro-7-(4-fluoro-2-methoxyphenoxy)-8-methyl-2-naphthonitrile

Conditions	Yield
With copper(l) iodide; 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate In 1,4-dioxane Inert atmosphere; Sealed tube; Heating;	78%

bis(tri-t-butylphosphine)palladium(0) (53199-31-8) + dichloromethane (75-09-2) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + 1,3-bis(cyclohexylphosphanyl)propane (97472-13-4) → C34H56BrFOP2Pd*0.62CH2Cl2

Conditions	Yield
Stage #1: bis(tri-t-butylphosphine)palladium(0); 1,3-bis(cyclohexylphosphanyl)propane In toluene at 20℃; for 1h; Inert atmosphere; Stage #2: 1-bromo-4-fluoro-2-methoxybenzene In toluene at 80℃; for 15h; Inert atmosphere; Stage #3: dichloromethane	76%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + 4-Methoxybenzyl alcohol (105-13-5) → C15H15BrO3 (949019-87-8)

Conditions	Yield
Stage #1: 4-Methoxybenzyl alcohol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: 1-bromo-4-fluoro-2-methoxybenzene In N,N-dimethyl-formamide; mineral oil at 100℃; Inert atmosphere;	75%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + (S)-2,2'-diamino-1,1'-binaphthalene (18531-95-8) → C27H21FN2O

Conditions	Yield
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene; (S)-2,2'-diamino-1,1'-binaphthalene With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: With sodium tert-butoxide In toluene at 20 - 70℃; for 5.16667h; Schlenk technique; Inert atmosphere;	74.2%

8-fluoro-7-hydroxy-5-methyl-2-naphthonitrile + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 8-fluoro-7-(4-fluoro-2-methoxyphenoxy)-5-methyl-2-naphthonitrile

Conditions	Yield
With copper(l) iodide; 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate In 1,4-dioxane Inert atmosphere; Sealed tube; Heating;	74%

cyclobutanone (1191-95-3) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → C11H13FO2

Conditions	Yield
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.333333h; Inert atmosphere; Stage #2: cyclobutanone In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere;	71%

2,2-dimethylmalononitrile (7321-55-3) + 1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 4-(2-cyanopropan-2-yl)-2-methoxybenzonitrile

Conditions	Yield
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.0833333h; Stage #2: 2,2-dimethylmalononitrile In tetrahydrofuran; hexane at -78 - 20℃; for 1h;	70%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + t-butyl 4-hydroxy piperidine-1-carboxylate (109384-19-2) → C17H24BrNO4 (1173006-38-6)

Conditions	Yield
Stage #1: t-butyl 4-hydroxy piperidine-1-carboxylate With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: 1-bromo-4-fluoro-2-methoxybenzene In N,N-dimethyl-formamide; mineral oil at 100℃; Inert atmosphere;	69%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) → 4-fluoro-2-methoxybenzenethiol (398456-80-9)

Conditions	Yield
With tert.-butyl lithium; sulfur In tetrahydrofuran; pentane at -78℃; for 1h;	68%
With tert.-butyl lithium; sulfur In tetrahydrofuran; pentane at -78℃; for 1h;	68%

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 3-bromo-6-fluoro-2-methoxybenzaldehyde (473416-74-9)

Conditions	Yield
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78℃; for 0.833333h;	66%
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -78℃; for 1h;	64%
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1.25h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -78℃; for 0.833333h; Inert atmosphere;	9.7 g
Stage #1: 1-bromo-4-fluoro-2-methoxybenzene With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1.3h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexanes at -78℃; for 0.8h;

1-bromo-4-fluoro-2-methoxybenzene (450-88-4) + isopropyl alcohol (67-63-0) → 1-bromo-4-isopropoxy-2-methoxybenzene (176391-61-0)

Conditions	Yield
Stage #1: isopropyl alcohol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: 1-bromo-4-fluoro-2-methoxybenzene In N,N-dimethyl-formamide; mineral oil at 100℃; Inert atmosphere;	66%

Upstream product

• 2591-86-8 N-Formylpiperidine 
• 456-49-5 1-fluoro-3-methoxybenzene 
• 77-78-1 dimethyl sulfate 
• 147460-41-1 2-bromo-5-fluorophenol 
• 395-82-4 4-fluoro-2-methoxy-benzoic acid 
• 446-36-6 5-fluoro-2-nitrophenol 
• 446-35-5 2,4-Difluoronitrobenzene 
• 348-57-2 2,4-difluorobromobenzene 
• 865-33-8 potassium methanolate 
• 67-56-1 methanol 
• 74-88-4 methyl iodide 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 450-91-9 4-fluoro-2-methoxyaniline 

Downstream Products

• 473416-71-6 (3-bromo-6-fluoro-2-methoxy-phenyl)-naphthalen-2-yl-methanol 
• 473417-48-0 5-bromo-2-fluoro-4-methoxybenzaldehyde 
• 949019-87-8 C₁₅H₁₅BrO₃ 
• 958029-46-4 2-(5-bromo-2-fluoro-4-methoxyphenyl)propan-2-ol 
• 944317-92-4 1-bromo-4-fluoro-2-methoxy-5-(propan-2-yl)-benzene 
• 875548-97-3 (4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)-[1,1'-biphenyl]-2-yl)methanol 
• 914221-54-8 1-(5-bromo-2-fluoro-4-methoxyphenyl)ethan-1-one 
• 90531-98-9 1-bromo-2-methoxy-4-(methylsulfonyl)benzene 

Relevant articles and documents

Preparative scale synthesis of the biaryl core of anacetrapib via a ruthenium-catalyzed direct arylation reaction: Unexpected effect of solvent impurity on the arylation reaction

In this report, we disclose our findings regarding the remarkable effect of a low-level impurity found in the solvent used for a ruthenium-catalyzed direct arylation reaction. This discovery allowed for the development of a robust and high-yield arylation protocol that was demonstrated on a multikilogram scale using carboxylate as the cocatalyst. Finally, a practical, scalable, and chromatography-free synthesis of the biaryl core of Anacetrapib is described.(Figure Presented)

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Chemical Compounds

The present invention relates to imidazopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine derivatives of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are as defined in the description. The imidazopyridazine derivatives of the present invention modulate the activity of the GABAA receptor. They are useful in the treatment of a number of conditions, including pain.