189035-22-1

Basic information

• Product Name: 6-BROMO-2,3-DIHYDRO-BENZOFURAN
• Synonyms: 6-BROMO-2,3-DIHYDRO-BENZOFURAN;6-broMo-2,3-dihydro-1-benzofuran;6-Bromo-2,3-dihydrobenzo[b]furan
• CAS NO: 189035-22-1
• Molecular Formula: C₈H₇BrO
• Molecular Weight: 199.04458
• Mol File: 189035-22-1.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 239.8°C at 760 mmHg
• Flash Point: 94.9°C
• Appearance: /
• Density: 1.582g/cm³
• Vapor Pressure: 0.0607mmHg at 25°C
• Refractive Index: 1.601
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 6-BROMO-2,3-DIHYDRO-BENZOFURAN(CAS DataBase Reference)
• NIST Chemistry Reference: 6-BROMO-2,3-DIHYDRO-BENZOFURAN(189035-22-1)
• EPA Substance Registry System: 6-BROMO-2,3-DIHYDRO-BENZOFURAN(189035-22-1)

Safety Data

• Hazardous Substances Data: 189035-22-1(Hazardous Substances Data)

Usage

Uses

6-Bromo-2,3-dihydrobenzofuran is used in the preparation of 2-alkylamino nicotinamide analogs as orally active ghrelin receptor (ghrelinR) inverse agonists.

InChI:InChI=1/C8H7BrO/c9-7-2-1-6-3-4-10-8(6)5-7/h1-2,5H,3-4H2

Synthetic route

1,4-dibromo-2-(2-bromoethoxy)benzene (377091-18-4) → 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 4h;	94%
With n-butyllithium In tetrahydrofuran; benzene at -78℃; for 1h; Inert atmosphere;	85%
With n-butyllithium In tetrahydrofuran; benzene at -78℃; for 1h; Inert atmosphere;	85%

1,4-dibromo-2-hydroxyethoxybenzene (377091-17-3) → 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1)

Conditions	Yield
Stage #1: 1,4-dibromo-2-hydroxyethoxybenzene With phosphorus tribromide In toluene at 90℃; for 2.5h; Heating / reflux; Stage #2: With sodium hydroxide In water; toluene at 20℃; Stage #3: With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 0.5h;	40%
Multi-step reaction with 2 steps 1: phosphorus tribromide / toluene / 10 h / 90 °C 2: n-butyllithium / tetrahydrofuran; benzene / 1 h / -78 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: phosphorus tribromide / toluene / 2.5 h / 20 - 90 °C 2: n-butyllithium / tetrahydrofuran; hexane / 2.5 h / -78 - 0 °C / Inert atmosphere View Scheme

2,3-Dihydrobenzofuran (496-16-2) → 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1)

Conditions	Yield
With potassium hydroxide; bromine; potassium bromide at 20℃;

2-trimethylstannyl-1,3-cyclohexadiene + Br2 -solution → 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1)

Conditions	Yield
In n-heptane; dichloromethane; ethyl acetate

2,5-dibromophenol (28165-52-8) → 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / 40 h / 80 °C 2: n-butyllithium / hexane; tetrahydrofuran / 4 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 4 h / 80 °C 2: n-butyllithium / tetrahydrofuran / 3 h / -100 °C View Scheme

2,5-dibromofluorobenzene (1435-52-5) → 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1-methyl-pyrrolidin-2-one; potassium tert-butylate / 100 °C / Inert atmosphere 2: phosphorus tribromide / toluene / 10 h / 90 °C 3: n-butyllithium / tetrahydrofuran; benzene / 1 h / -78 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 100 °C / Inert atmosphere 2: phosphorus tribromide / toluene / 10 h / 90 °C 3: n-butyllithium / tetrahydrofuran; benzene / 1 h / -78 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: potassium tert-butylate; 1-methyl-pyrrolidin-2-one / 15 h / 20 - 100 °C 2: phosphorus tribromide / toluene / 2.5 h / 20 - 90 °C 3: n-butyllithium / tetrahydrofuran; hexane / 2.5 h / -78 - 0 °C / Inert atmosphere View Scheme

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 5,6-dibromo-2,3-dihydro-1-benzofuran (1102467-17-3)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 20℃; for 3h;	93%
With N-Bromosuccinimide In acetonitrile at 20℃;

potassium cyanide + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → C9H7NO

Conditions	Yield
Stage #1: potassium cyanide With acetic acid In ethylene glycol at 20℃; Sealed tube; Stage #2: 6-bromo-2,3-dihydro-1-benzofuran With P(t-Bu)3 Palladacycle Gen. 3; potassium acetate In 1,4-dioxane; water at 60℃; for 16h; Sealed tube;	93%

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-oxocyclopenta-1,3-dieno[2,1-b]pyridine (496047-46-2) → 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-5-hydroxy-5H-cyclopenta[b]pyridine (721965-55-5)

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium In tetrahydrofuran Stage #2: 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-oxocyclopenta-1,3-dieno[2,1-b]pyridine In tetrahydrofuran at -78℃; for 1h; Grignard reaction;	89%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 2,3-dihydro-1-benzofuran-6-carbaldehyde (55745-96-5)

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium In 2-methyltetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In 2-methyltetrahydrofuran; hexane at -78℃; for 2h;	85%
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 0.5h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at 20℃; for 0.75h;	79%
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;	52%

2-ethylhexyl 3-sulfanylpropanoate (50448-95-8) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 2-ethylhexyl 3-(2,3-dihydro-1-benzofuran-6-ylthio)propanoate (1156468-65-3)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; for 10h; Inert atmosphere;	83%
With N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; for 10h;	33%

pinacol vinylboronate (75927-49-0) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 6-vinyl-2,3-dihydrobenzofuran

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 105℃; for 16h;	79.4%

formaldehyd (50-00-0) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → (2,3-dihydrobenzofuran-6-yl)methanol (1083168-69-7)

Conditions	Yield
With tert.-butyl lithium In tetrahydrofuran; pentane at -74 - 20℃; Inert atmosphere;	74%

tributyl(1-ethoxyvinyl)stannane (97674-02-7) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 1-(2,3-dihydrobenzofuran-6-yl)ethan-1-one (374706-07-7)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride In toluene at 90℃; for 16h;	73.7%

oxirene (157-18-6) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 2-(2,3-dihydrobenzofuran-6-yl)ethan-1-ol

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With iodine; magnesium In tetrahydrofuran at 20 - 70℃; for 1h; Inert atmosphere; Stage #2: oxirene In tetrahydrofuran at 20℃; for 2h;	64.3%

Dimethyldisulphide (624-92-0) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 6-(methylthio)-2,3-dihydro-1-benzofuran (1102467-20-8)

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium In tetrahydrofuran; hexanes at -78℃; for 0.5h; Stage #2: Dimethyldisulphide In tetrahydrofuran; hexanes for 1h;	62%

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + 2-(N-benzylisopropylamino)-6-chloro-5-{(E)-[2-(4S,5S)-4-methoxymethyl-5-(4-methylthiophenyl)-4,5-dihydro-1,3-oxazol-2-yl]vinyl}pyridine (464170-04-5) → (3S)-3-[6-(N-benzyl-N-isopropylamino)-2-chloro-3-pyridinyl]-3-(2,3-dihydro-1-benzofuran-6-yl)propanoic acid (464170-05-6)

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 2-(N-benzylisopropylamino)-6-chloro-5-{(E)-[2-(4S,5S)-4-methoxymethyl-5-(4-methylthiophenyl)-4,5-dihydro-1,3-oxazol-2-yl]vinyl}pyridine In tetrahydrofuran; hexane at -78℃; for 1h; Stage #3: With sulfuric acid In 1,4-dioxane; water at 100℃; for 1.5h;	60%

2-(6-trifluoromethyl-pyridin-3-yl)-ethylamine (765287-34-1) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → (2,3-dihydro-benzofuran-6-yl)-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amine (1201195-88-1)

Conditions	Yield
With caesium carbonate; copper(l) iodide; 2-acetylcyclohexanone In N,N-dimethyl-formamide at 120℃; for 2h; Inert atmosphere;	52%

tert-butyl 2-oxopyrrolidine-1-carboxylate (85909-08-6) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → tert-butyl (4-(2,3-dihydrobenzofuran-6-yl)-4-oxobutyl)carbamate

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium; lithium chloride In tetrahydrofuran; ethylene dibromide at 65℃; for 2h; Stage #2: tert-butyl 2-oxopyrrolidine-1-carboxylate In tetrahydrofuran; ethylene dibromide at -78℃; for 2h;	37%

3-(((4-methoxybenzyl)(methyl)amino)methyl)-2-methylbenzofuran-7-ol + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 1-(7-((2,3-dihydrobenzofuran-6-yl)oxy)-2-methylbenzofuran-3-yl)-N-(4-methoxybenzyl)-N-methylmethanamine

Conditions	Yield
With potassium phosphate; copper(l) iodide; dimethylaminoacetic acid In dimethyl sulfoxide at 110℃; for 16h;	27%

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + Benzyl-(6-bromo-5-{(E)-2-[(4S,5S)-4-methoxymethyl-5-(4-methylsulfanyl-phenyl)-4,5-dihydro-oxazol-2-yl]-vinyl}-pyridin-2-yl)-isopropyl-amine → (S)-3-[6-(Benzyl-isopropyl-amino)-2-bromo-pyridin-3-yl]-3-(2,3-dihydro-benzofuran-6-yl)-propionic acid

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium In tetrahydrofuran; hexane at -78℃; Stage #2: Benzyl-(6-bromo-5-{(E)-2-[(4S,5S)-4-methoxymethyl-5-(4-methylsulfanyl-phenyl)-4,5-dihydro-oxazol-2-yl]-vinyl}-pyridin-2-yl)-isopropyl-amine In tetrahydrofuran; hexane at -78℃; Stage #3: With sulfuric acid In 1,4-dioxane; water at 100℃;

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + (S)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4-isopropyl-oxazolidin-2-one (494841-72-4) → (S)-3-[3-(2-Chloro-pyridin-3-yl)-3-(2,3-dihydro-benzofuran-6-yl)-propionyl]-4-isopropyl-oxazolidin-2-one

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium In tetrahydrofuran at 70℃; for 2h; Stage #2: With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at 5℃; for 0.333333h; Stage #3: (S)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4-isopropyl-oxazolidin-2-one In tetrahydrofuran at -78℃; for 1h; Michael addition;

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + (S)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4-phenyl-oxazolidin-2-one (494841-70-2) → (S)-3-[3-(2-Chloro-pyridin-3-yl)-3-(2,3-dihydro-benzofuran-6-yl)-propionyl]-4-phenyl-oxazolidin-2-one

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium In tetrahydrofuran at 70℃; for 2h; Stage #2: With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at 5℃; for 0.333333h; Stage #3: (S)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4-phenyl-oxazolidin-2-one In tetrahydrofuran at -78℃; for 1h; Michael addition;

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + (4S,5R)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4-methyl-5-phenyl-oxazolidin-2-one (494841-71-3) → (4S,5R)-3-[3-(2-Chloro-pyridin-3-yl)-3-(2,3-dihydro-benzofuran-6-yl)-propionyl]-4-methyl-5-phenyl-oxazolidin-2-one

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium In tetrahydrofuran at 70℃; for 2h; Stage #2: With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at 5℃; for 0.333333h; Stage #3: (4S,5R)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4-methyl-5-phenyl-oxazolidin-2-one In tetrahydrofuran at -78℃; for 1h; Michael addition;

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + (R)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-5,5-dimethyl-4-phenyl-oxazolidin-2-one (494841-73-5) → (R)-3-[3-(2-Chloro-pyridin-3-yl)-3-(2,3-dihydro-benzofuran-6-yl)-propionyl]-5,5-dimethyl-4-phenyl-oxazolidin-2-one

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium In tetrahydrofuran at 70℃; for 2h; Stage #2: With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at 5℃; for 0.333333h; Stage #3: (R)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-5,5-dimethyl-4-phenyl-oxazolidin-2-one In tetrahydrofuran at -78℃; for 1h; Michael addition;

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + 2-chloro-3-{(E)-[2-(4S,5S)-4-methoxymethyl-5-(4-methylthiophenyl)-4,5-dihydro-1,3-oxazol-2-yl]vinyl}pyridine (494841-80-4) → 2-Chloro-3-{1-(2,3-dihydro-benzofuran-6-yl)-2-[(4S,5S)-4-methoxymethyl-5-(4-methylsulfanyl-phenyl)-4,5-dihydro-oxazol-2-yl]-ethyl}-pyridine

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: 2-chloro-3-{(E)-[2-(4S,5S)-4-methoxymethyl-5-(4-methylthiophenyl)-4,5-dihydro-1,3-oxazol-2-yl]vinyl}pyridine In tetrahydrofuran; hexane at -78℃;	76 % Chromat.

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) + (4R,5S)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4,5-diphenyl-oxazolidin-2-one (494841-74-6) → (4R,5S)-3-[3-(2-Chloro-pyridin-3-yl)-3-(2,3-dihydro-benzofuran-6-yl)-propionyl]-4,5-diphenyl-oxazolidin-2-one

Conditions	Yield
Stage #1: 6-bromo-2,3-dihydro-1-benzofuran With magnesium In tetrahydrofuran at 70℃; for 2h; Stage #2: With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at 5℃; for 0.333333h; Stage #3: (4R,5S)-3-[(E)-3-(2-Chloro-pyridin-3-yl)-acryloyl]-4,5-diphenyl-oxazolidin-2-one In tetrahydrofuran at -78℃; for 1h; Michael addition;

ethyl acrylate (140-88-5) + 6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → (E)-3-(2,3-Dihydro-benzofuran-6-yl)-acrylic acid ethyl ester

Conditions	Yield
With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine In acetonitrile at 90℃;

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 5-(2,3-dihydro-benzofuran-6-yl)-7-(2-hydroxy-4-methoxy-phenyl)-6,7-dihydro-5H-[1]pyrindine-6-carboxylic acid tert-butyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1.1: Mg / tetrahydrofuran 1.2: 89 percent / tetrahydrofuran / 1 h / -78 °C 2.1: 4-(dimethylamino)pyridine / CHCl3 / 1 h / 20 °C 3.1: 189 g / H2; NaHCO3 / Pd(OH)2/C / tetrahydrofuran; ethanol / 45 h / 20 °C / 760 Torr 4.1: potassium tert-butoxide / tetrahydrofuran; 2-methyl-propan-2-ol / 0.33 h / 0 °C View Scheme

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → (5RS,6RS,7SR)-7-(2-hydroxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine

Conditions	Yield
Multi-step reaction with 3 steps 1.1: Mg / tetrahydrofuran 1.2: 89 percent / tetrahydrofuran / 1 h / -78 °C 2.1: 4-(dimethylamino)pyridine / CHCl3 / 1 h / 20 °C 3.1: 189 g / H2; NaHCO3 / Pd(OH)2/C / tetrahydrofuran; ethanol / 45 h / 20 °C / 760 Torr View Scheme

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → 5-(2,3-dihydro-benzofuran-6-yl)-7-(4-methoxy-2-vinyl-phenyl)-6,7-dihydro-5H-[1]pyrindine-6-carboxylic acid tert-butyl ester

Conditions

Yield

Multi-step reaction with 6 steps 1.1: Mg / tetrahydrofuran 1.2: 89 percent / tetrahydrofuran / 1 h / -78 °C 2.1: 4-(dimethylamino)pyridine / CHCl3 / 1 h / 20 °C 3.1: 189 g / H2; NaHCO3 / Pd(OH)2/C / tetrahydrofuran; ethanol / 45 h / 20 °C / 760 Torr 4.1: potassium tert-butoxide / tetrahydrofuran; 2-methyl-propan-2-ol / 0.33 h / 0 °C 5.1: 172 g / 4-(dimethylamino)pyridine / CHCl3 / 0.5 h / 0 °C 6.1: dichloro[bis(triphenylphosphine)]palladium; LiCl / dimethylformamide / 4 h / 125 °C 6.2: 112 g / KF / dimethylformamide; H2O; ethyl acetate / 0.5 h / 20 °C View Scheme

6-bromo-2,3-dihydro-1-benzofuran (189035-22-1) → (5RS,6SR,7SR)-7-(2-hydroxymethyl-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-6,7-dihydro-5H-cyclopenta[b]pyridine

Conditions

Yield

Multi-step reaction with 8 steps 1.1: Mg / tetrahydrofuran 1.2: 89 percent / tetrahydrofuran / 1 h / -78 °C 2.1: 4-(dimethylamino)pyridine / CHCl3 / 1 h / 20 °C 3.1: 189 g / H2; NaHCO3 / Pd(OH)2/C / tetrahydrofuran; ethanol / 45 h / 20 °C / 760 Torr 4.1: potassium tert-butoxide / tetrahydrofuran; 2-methyl-propan-2-ol / 0.33 h / 0 °C 5.1: 172 g / 4-(dimethylamino)pyridine / CHCl3 / 0.5 h / 0 °C 6.1: dichloro[bis(triphenylphosphine)]palladium; LiCl / dimethylformamide / 4 h / 125 °C 6.2: 112 g / KF / dimethylformamide; H2O; ethyl acetate / 0.5 h / 20 °C 7.1: OsO4; 4-methylmorpholine N-oxide / tetrahydrofuran; H2O / 12 h / 20 °C 8.1: NaIO4; 4-methylmorpholine N-oxide / tetrahydrofuran; H2O / 0.33 h / 0 °C 8.2: 84.2 g / NaBH4 / tetrahydrofuran; H2O / 0.33 h / 20 °C View Scheme

Upstream product

• 496-16-2 2.3-dihydrobenzofuran 
• 28165-52-8 2,5-dibromophenol 
• 1435-52-5 2,5-dibromofluorobenzene 
• 377091-18-4 1,4-dibromo-2-(2-bromoethoxy)benzene 
• 377091-17-3 1,4-dibromo-2-hydroxyethoxybenzene 

Downstream Products

• 917815-18-0 {4-[(2R,3R)-3-[2-(2,3-dihydro-benzofuran-6-yl)-2-oxo-ethylsulfanyl]-1-(4-fluoro-phenyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid tert-butyl ester 
• 917815-08-8 {4-[(2R,3R)-3-[2-(2,3-dihydro-benzofuran-6-yl)-2-oxo-ethylsulfanyl]-1-(4-fluoro-phenyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid 
• 374706-07-7 1-(2,3-dihydrobenzofuran-6-yl)ethan-1-one 
• 1083168-69-7 (2,3-dihydrobenzofuran-6-yl)methanol 
• 55746-20-8 (2,3-dihydrobenzofuran-6-yl)methanamine 
• 1345120-28-6 N-[5-(5-chloro-2,3-dihydrobenzo[b]furan-6-yl)pyrazin-2-yl](2,6-difluorophenyl)carboxamide 
• 1345120-21-9 N-[5-(5-chloro(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)](2-fluorophenyl)carboxamide 
• 1345120-15-1 N-[5-(5-chloro(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)](2,6-difluorophenyl)carboxamide 
• 1345119-98-3 N-[5-(5-bromo(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)](2-fluorophenyl)carboxamide 
• 1345119-92-7 N-[5-(5-bromo(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)](2,6-difluorophenyl)carboxamide 
• 55745-96-5 2,3-dihydro-1-benzofuran-6-carbaldehyde 

Relevant articles and documents

5,5-DIFLUORO- AND 5-FLUORO-5-METHYL-C-GLYCOSIDE DERIVATIVES USEFUL AS DUAL SGLT1 / SGLT2 MODULATORS

The present invention is directed to 5,5-difluoro- and 5-fluoro-5-methyl-C-glycoside derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by SGLT activity, more particularly dual SGLT1/2 activity.

COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF

The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.

Orally active ghrelin receptor inverse agonists and their actions on a rat obesity model

A series of 2-alkylamino nicotinamide analogs was prepared as orally active ghrelin receptor (ghrelinR) inverse agonists. Starting from compound 1, oral bioavailability was improved by modifying metabolically unstable sites and reducing molecular weight. Brain-permeable compound 33 and compound 24 with low brain permeability were tested in rat models of obesity; 30 mg/kg of compound 33 suppressed weight gain. PK/PD analysis revealed that the anti-obesity effect of ghrelinR inverse agonists depends on their brain concentrations.