1132832-75-7

Basic information

• Product Name: (5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone
• Synonyms: (5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone;2-(5-BroMo-2-Methylbenzoyl)-5-(4-fluorophenyl)thiophene;(5-broMo-2-Methylphenyl)[5-(4-fluorophenyl)-2-thienyl]- Methanone;Methanone, (5-BroMo-2-Methylphenyl)[5-(4-fluorophenyl)-2-thienyl]-;Canagliflozin iMpurity B;Canagliflozin INT1;(5-bromo-2-methylphenyl)[5-(4-flurophenyl)-2-thienyl]-methanone
• CAS NO: 1132832-75-7
• Molecular Formula: C₁₈H₁₂BrFOS
• Molecular Weight: 375.2546832
• EINECS: 1308068-626-2
• Mol File: 1132832-75-7.mol

Chemical Properties

• Boiling Point: 476.0±45.0 °C(Predicted)
• Appearance: /
• Density: 1.448±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)
• Solubility: DMSO (Slightly)
• CAS DataBase Reference: (5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone(CAS DataBase Reference)
• NIST Chemistry Reference: (5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone(1132832-75-7)
• EPA Substance Registry System: (5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone(1132832-75-7)

Safety Data

• Hazardous Substances Data: 1132832-75-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone is used as an intermediate in the preparation of Canagliflozin, a medication for the treatment of type 2 diabetes. Canagliflozin is a sodium-dependent glucose co-transporter 2 (SGLT2) inhibitor that helps lower blood sugar levels by preventing glucose reabsorption in the kidneys and promoting its excretion through urine. (5-broMo-2-Methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)Methanone plays a crucial role in the development and production of Canagliflozin, contributing to the management of type 2 diabetes and improving the quality of life for patients.

Synthetic route

2-(4-fluorophenyl)thiophene (58861-48-6) + 5-bromo-2-methylbenzoic acid (79669-49-1) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Stage #1: 5-bromo-2-methylbenzoic acid With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 20 - 25℃; Stage #2: 2-(4-fluorophenyl)thiophene With aluminum (III) chloride In dichloromethane at 0 - 25℃; for 12.5h; Solvent; Reagent/catalyst;	93.2%
Stage #1: 5-bromo-2-methylbenzoic acid With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 0 - 35℃; Stage #2: 2-(4-fluorophenyl)thiophene With aluminum (III) chloride In dichloromethane; N,N-dimethyl-formamide at 0 - 35℃;	89%
Stage #1: 5-bromo-2-methylbenzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 25 - 30℃; for 0.1h; Inert atmosphere; Stage #2: 2-(4-fluorophenyl)thiophene With aluminum (III) chloride In dichloromethane at 0 - 15℃; Inert atmosphere;	80.4%
Stage #1: 5-bromo-2-methylbenzoic acid With oxalyl dichloride In dichloromethane at 20℃; for 2h; Stage #2: 2-(4-fluorophenyl)thiophene With aluminum (III) chloride In dichloromethane at -15 - 35℃; for 4h;	80%

2-(4-fluorophenyl)thiophene (58861-48-6) + 5-bromo-2-methylbenzoyl chloride (21900-41-4) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at -10 - 25℃; for 5.5h; Friedel-Crafts Acylation; Inert atmosphere;	90.1%
With aluminum (III) chloride In dichloromethane at 0 - 20℃; Friedel Crafts acylation;	85.7%
Stage #1: 2-(4-fluorophenyl)thiophene; 5-bromo-2-methylbenzoyl chloride With aluminum (III) chloride In dichloromethane at -10 - 20℃; for 2.5 - 3.5h; Stage #2: With hydrogenchloride; water In n-heptane; dichloromethane at -12℃;
Stage #1: 2-(4-fluorophenyl)thiophene; 5-bromo-2-methylbenzoyl chloride With aluminum (III) chloride In dichloromethane at 0 - 20℃; Stage #2: With water In tetrahydrofuran cooling with ice;

1-Bromo-4-fluorobenzene (460-00-4) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / tricyclohexylphosphine; tris-(dibenzylideneacetone)dipalladium(0) / ethanol; water / 90 °C / Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 0 - 20 °C 2.2: cooling with ice View Scheme
Multi-step reaction with 4 steps 1: potassium acetate; palladium diacetate / N,N-dimethyl acetamide / 22 h / 140 - 150 °C 2: sodium dihydrogenphosphate; dihydrogen peroxide; sodium chlorite / acetonitrile; water / 1.5 h / 40 °C 3: thionyl chloride / toluene / 21 h / 90 °C 4: iron(III) chloride / dichloromethane / 20 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium propionate; bis[di-t-butyl(p-dimethylaminophenyl)phosphino]palladium (II) Dichloride / Isopropyl acetate / Reflux 2.1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / Dimethyl ether; water / 70 - 75 °C 3.1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / 0 - 35 °C 3.2: 0 - 35 °C View Scheme

5-bromo-2-methylbenzoic acid (79669-49-1) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 6 h / 20 °C 2.1: aluminum (III) chloride / dichloromethane / 0 - 20 °C 2.2: cooling with ice View Scheme
Multi-step reaction with 2 steps 1.1: dicyclohexyl-carbodiimide; 1-hydroxybenzotriazol-hydrate; triethylamine / dichloromethane / 20 °C / Inert atmosphere 2.1: hydrogenchloride; magnesium; iodine / diethyl ether / 0.33 h / Inert atmosphere; Reflux 2.2: 20 °C / Inert atmosphere View Scheme

5-(4-fluorophenyl)thiophene-2-carboxylic acid (115933-30-7) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / toluene / 21 h / 90 °C 2: iron(III) chloride / dichloromethane / 20 h / 20 °C View Scheme

5-(4-fluorophenyl)thiophene-2-carbonyl chloride (918487-45-3) + para-bromotoluene (106-38-7) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
With iron(III) chloride In dichloromethane at 20℃; for 20h;	0.77 g

thiophene-2-carbaldehyde (98-03-3) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium acetate; palladium diacetate / N,N-dimethyl acetamide / 22 h / 140 - 150 °C 2: sodium dihydrogenphosphate; dihydrogen peroxide; sodium chlorite / acetonitrile; water / 1.5 h / 40 °C 3: thionyl chloride / toluene / 21 h / 90 °C 4: iron(III) chloride / dichloromethane / 20 h / 20 °C View Scheme

5-(4-fluorophenyl)thiophene-2-carboxaldehyde (249504-38-9) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium dihydrogenphosphate; dihydrogen peroxide; sodium chlorite / acetonitrile; water / 1.5 h / 40 °C 2: thionyl chloride / toluene / 21 h / 90 °C 3: iron(III) chloride / dichloromethane / 20 h / 20 °C View Scheme

4-fluoroboronic acid (1765-93-1) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / 1,2-dimethoxyethane; water / 25 - 75 °C / Inert atmosphere 2.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.1 h / 25 - 30 °C / Inert atmosphere 2.2: 0 - 15 °C / Inert atmosphere View Scheme

2-bromo-5-(4-fluorophenyl)thiophene (1073313-97-9) + 5-bromo-N-methoxy-N,2-dimethylbenzamide (842135-03-9) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Stage #1: 2-bromo-5-(4-fluorophenyl)thiophene With hydrogenchloride; iodine; magnesium In diethyl ether for 0.333333h; Inert atmosphere; Reflux; Stage #2: 5-bromo-N-methoxy-N,2-dimethylbenzamide In tetrahydrofuran; diethyl ether at 20℃; Inert atmosphere;	0.402 g

fluorobenzene (462-06-6) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 2 h / Cooling with ice; Reflux 2.1: tetraphosphorus decasulfide / toluene / 0.5 h / Microwave irradiation 3.1: oxalyl dichloride / dichloromethane / 2 h / 20 °C 3.2: 4 h / -15 - 35 °C View Scheme

4-(4-fluorophenyl)-4-oxopropionic acid (366-77-8) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetraphosphorus decasulfide / toluene / 0.5 h / Microwave irradiation 2.1: oxalyl dichloride / dichloromethane / 2 h / 20 °C 2.2: 4 h / -15 - 35 °C View Scheme

2-(4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (214360-58-4) → (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / Dimethyl ether; water / 70 - 75 °C 2.1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / 0 - 35 °C 2.2: 0 - 35 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → 2-[(5-bromo-2-methyl-phenyl)methyl]-5-(4-fluorophenyl)thiophene (1030825-20-7)

Conditions	Yield
With borane-THF In tetrahydrofuran at -20 - -10℃; for 48h; Reagent/catalyst; Temperature; Concentration; Solvent;	97.7%
With hydrogen In isopropyl alcohol at 100℃; under 22502.3 Torr; for 5h; Reagent/catalyst; Temperature; Pressure; Autoclave;	97%
Stage #1: (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone With aluminum (III) chloride In tetrahydrofuran at 0 - 5℃; for 0.5h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran Reflux;	92%

methanesulfonic acid (75-75-2) + (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) + C14H18O10 → C33H33FO11S

Conditions	Yield
Stage #1: (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone With n-butyllithium In tetrahydrofuran; N,N-dimethyl-formamide at -50 - -40℃; for 3h; Inert atmosphere; Stage #2: C14H18O10 In tetrahydrofuran; N,N-dimethyl-formamide for 8h; Inert atmosphere; Stage #3: methanesulfonic acid In tetrahydrofuran at 20℃;	85.8%

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → (5-bromo-2-[D3]methylphenyl)(5-(4-fluorophenyl)thiophen-2-yl)ketone

Conditions	Yield
With [D]-sodium hydroxide In water-d2 at 160℃; for 8h;	84%

methanesulfonic acid (75-75-2) + (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) + C10H18O14S4 → C29H33FO15S5

Conditions	Yield
Stage #1: (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone With potassium hexamethylsilazane In tetrahydrofuran; toluene at -50 - -40℃; for 3h; Inert atmosphere; Stage #2: C10H18O14S4 In tetrahydrofuran; toluene for 8h; Inert atmosphere; Stage #3: methanesulfonic acid In tetrahydrofuran at 20℃;	83.9%

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → 2-(5-bromo-2-methyl[1,1-D2]benzyl)-5-(4-fluorophenyl)thiophene

Conditions	Yield
With aluminum (III) chloride; sodium borodeuteride In acetonitrile at 55℃; for 0.166667h; Inert atmosphere;	82%

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → (1R,4R,5S,6R)-4,5,6-tris(benzyloxy)-3-(benzyloxymethyl)-1-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)cyclohex-2-enol (1413373-77-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane; acetonitrile / 3 h / 0 - 20 °C 2.1: n-butyllithium / toluene; hexane; tetrahydrofuran / 0.08 h / -70 °C / Inert atmosphere 2.2: 0.25 h / -70 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → (3R,4S,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (1030825-21-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride; sodium tetrahydroborate / 1,2-dimethoxyethane / 0 - 70 °C 2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / -75 - -65 °C / Inert atmosphere 2.2: -75 - -70 °C 2.3: 12 h / -75 - 30 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → canagliflozin (842133-18-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride; sodium tetrahydroborate / 1,2-dimethoxyethane / 0 - 70 °C 2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / -75 - -65 °C / Inert atmosphere 2.2: -75 - -70 °C 2.3: 12 h / -75 - 30 °C 3.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane / 0 - 5 °C View Scheme
Multi-step reaction with 4 steps 1.1: 0.25 h / 20 °C 1.2: 50 - 60 °C 2.1: iodine; magnesium / tetrahydrofuran / 25 - 35 °C / Inert atmosphere 2.2: 2 h / 0 - 5 °C / Inert atmosphere 3.1: methanesulfonic acid / water / 20 °C 4.1: triethylsilane / acetonitrile; dichloromethane / 0.25 h / 0 - 5 °C / Inert atmosphere 4.2: 0 - 30 °C / Inert atmosphere View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (866607-35-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride; sodium tetrahydroborate / 1,2-dimethoxyethane / 0 - 70 °C 2.1: n-butyllithium / tetrahydrofuran; toluene; hexane / -75 - -65 °C / Inert atmosphere 2.2: -75 - -70 °C 2.3: 12 h / -75 - 30 °C 3.1: boron trifluoride diethyl etherate; triethylsilane / dichloromethane / 0 - 5 °C 4.1: dmap / acetone / 5 h / 0.25 - 0.5 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → (2S,3R,4R,5S,6R)-2-3-((5-(4-fluorophenyl)thiophen-[1,1-D2]methyl)-4-methylphenyl)-6-(hydroxymethyl)-tetrahydro-2H-pyrantriol

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride; sodium borodeuteride / acetonitrile / 0.17 h / 55 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; toluene / 0.55 h / -78 - -66 °C / Inert atmosphere 2.2: 5 h / -78 - -60 °C 3.1: triethylsilane; boron trifluoride diethyl etherate / dichloromethane / -50 - 20 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → (3R,4S,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)[1,1-D2]methyl)-4-methylphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Conditions	Yield
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride; sodium borodeuteride / acetonitrile / 0.17 h / 55 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; toluene / 0.55 h / -78 - -66 °C / Inert atmosphere 2.2: 5 h / -78 - -60 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → 2-(5-bromo-2-[D3]methylbenzyl)-5-(4-fluorophenyl)thiophene

Conditions	Yield
Multi-step reaction with 2 steps 1: [D]-sodium hydroxide / water-d2 / 8 h / 160 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 55 °C / Inert atmosphere View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) + trimethyl orthoformate (149-73-5) → 2-[(5-bromo-2-methylphenyl)(dimethoxy)methyl]-5-(4-fluorophenyl)thiophene

Conditions	Yield
Stage #1: (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone; trimethyl orthoformate at 20℃; for 0.25h; Stage #2: With toluene-4-sulfonic acid In methanol at 50 - 60℃;

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → [5-(4-fluorophenyl)-thiophen-2-yl]-[2-methyl-5-(3,4,5-trihydroxy-6-hydroxymethyl-2-methoxy-tetrahydropyran-2-yl)-phenyl]methanone

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 0.25 h / 20 °C 1.2: 50 - 60 °C 2.1: iodine; magnesium / tetrahydrofuran / 25 - 35 °C / Inert atmosphere 2.2: 2 h / 0 - 5 °C / Inert atmosphere 3.1: methanesulfonic acid / water / 20 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → C32H33FO9S

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / N,N-dimethyl-formamide; tetrahydrofuran / 3 h / -50 - -40 °C / Inert atmosphere 1.2: 8 h / Inert atmosphere 1.3: 20 °C 2.1: sodium tetrahydroborate; aluminum (III) chloride / tetrahydrofuran; methanol / 25 - 60 °C 2.2: Inert atmosphere View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]glucitol

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / N,N-dimethyl-formamide; tetrahydrofuran / 3 h / -50 - -40 °C / Inert atmosphere 1.2: 8 h / Inert atmosphere 1.3: 20 °C 2.1: sodium tetrahydroborate; aluminum (III) chloride / tetrahydrofuran; methanol / 25 - 60 °C 2.2: Inert atmosphere 3.1: lithium hydroxide; water / methanol / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 3 h / -50 - -40 °C / Inert atmosphere 1.2: 8 h / Inert atmosphere 1.3: 20 °C 2.1: lithium borohydride; aluminum (III) chloride / tetrahydrofuran; methanol / 25 - 60 °C 2.2: -30 - 20 °C / Inert atmosphere 3.1: sodium hydroxide; water / tetrahydrofuran / 20 °C View Scheme

(5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone (1132832-75-7) → C28H33FO13S5

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 3 h / -50 - -40 °C / Inert atmosphere 1.2: 8 h / Inert atmosphere 1.3: 20 °C 2.1: lithium borohydride; aluminum (III) chloride / tetrahydrofuran; methanol / 25 - 60 °C 2.2: -30 - 20 °C / Inert atmosphere View Scheme

Upstream product

• 115933-30-7 5-(4-fluorophenyl)thiophene-2-carboxylic acid 
• 918487-45-3 5-(4-fluorophenyl)thiophene-2-carbonyl chloride 
• 106-38-7 para-bromotoluene 
• 98-03-3 thiophene-2-carbaldehyde 
• 249504-38-9 5-(4-fluorophenyl)thiophene-2-carboxaldehyde 
• 214360-58-4 2-(4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 366-77-8 4-(4-fluorophenyl)-4-oxopropionic acid 
• 462-06-6 fluorobenzene 
• 1073313-97-9 2-bromo-5-(4-fluorophenyl)thiophene 
• 842135-03-9 5-bromo-N-methoxy-N,2-dimethylbenzamide 
• 58861-48-6 2-(4-fluorophenyl)thiophene 
• 79669-49-1 5-bromo-2-methylbenzoic acid 
• 1765-93-1 4-fluoroboronic acid 
• 460-00-4 1-Bromo-4-fluorobenzene 

Downstream Products

• 1030825-20-7 3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl bromide 
• 1413373-77-9 (1R,4R,5S,6R)-4,5,6-tris(benzyloxy)-3-(benzyloxymethyl)-1-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)cyclohex-2-enol 
• 1030825-21-8 methyl 1-C-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methyl-phenyl)-D-glucopyranoside 
• 842133-18-0 canagliflozin 
• 866607-35-4 (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 1589590-87-3 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]glucitol 

Relevant articles and documents

Preparation method of intermediate

The invention discloses a preparation method for a Canagliflozin intermediate. The preparation method comprises the steps that substituted bromobenzene as a starting material is reacted with bisdiboron to prepare a boride, and then the Canagliflozin intermediate is prepared through a Suzuki coupling reaction, a Friedel-Crafts acylation reaction and a reduction reaction. The preparation method hasthe advantages that the intermediate product CZ-2 is prepared through the Suzuki coupling reaction, the conditions are mild and easy to operate and control, and the product yield and the product purity are high; aryl methyl is introduced through the Friedel-Crafts acylation reaction, a main chain is built, by means of the route, the yield is high, technological conditions are easy to control, andthe preparation method is suitable for large-scale industrial production.

Preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene

The invention relates to the technical field of medicine synthesis, and particularly discloses a preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene. The preparation method comprises the following steps: by taking a nitrogen-doped carbon material loaded with transition metal as a catalyst, introducing hydrogen, and performing hydrogenation reduction on 2-methyl-5-bromophenyl-2-(4-fluorophenyl)thiophene ketone at 50-180 DEG C, thereby obtaining 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene. The preparation method provided by the invention has the characteristics of the high product yield, high purity, the low cost, no toxicity and no pollution, and overcomes the defects in the traditional preparation process of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene.

Synthesis method of canagliflozin intermediate

The invention relates to a synthesis method of a canagliflozin intermediate. Concretely, succinyl oxide and fluorobenzene are used as starting raw materials to be prepared into the canagliflozin crucial intermediate of 2-(4-fluorophenyl)-5-[(5-halogen-2-methyl phenyl)methyl]thiophene through the steps of Friedel-Crafts acylation ring opening, thiophene ring preparation, Friedel-Crafts acylation coupling, reduction and the like. The cheap succinyl oxide is used for preparing the thiophene ring, so that the Suzuki coupling reaction and Grignard reaction are avoided; the use of heavy metal reagents of palladium and the like is avoided; the production process is simplified; the product yield and the quality are improved; the environment pollution is reduced; the production cost is reduced.

A new SGLT2 inhibitor pharmaceutical preparation method

The invention discloses a preparation method for novel SGLT2 inhibitor medicine. The preparation method includes the steps that D-gluconolactone serves as an initial raw material and reacts with an acylation reagent under the action of a base to obtain a glucolactone intermediate with hydroxyl protection; 5-bromine-2-methyl benzoic acid is prepared into an acid chloride through an acylation reagent, and the acid chloride and 2-(4-fluoro-phenyl) thiophene perform friedel-Crafts acylation reaction under the action of Lewis acid; 2-(5-bromine-2-methyl-benzoyl)-5-(4-fluoro-phenyl) thiophene and the glucolactone intermediate perform electrophilic substitution reaction under the action of super-strong bases, and then etherification reaction is performed to obtain methyl etherate; the methyl etherate restores carbonyl into methylene under the action of a reducing agent, and an methoxy group is removed to form an S-configuration aromatic gluconolactone intermediate; the aromatic gluconolactone intermediate is hydrolyzed under the action of a base to obtain a canagliflozin product. The synthesis process route is short and simple, the quality of the intermediate is easy to control, the reaction yield is high, the production cost is low, and the preparation method is suitable for industrialized production.

Deuterium-modified carbon glycoside derivate

The invention belongs to the field of medinal chemistry and relates to a deuterium-modified carbon glycoside derivate, in particular to a compound shown in the formula I. The invention further relates to a preparation method of the deuterium-modified carbon glycoside derivate, a medicine composition comprising the deuterium-modified carbon glycoside derivate and application of the deuterium-modified carbon glycoside derivate or the medicine composition thereof for preparing medicine for treating diabetes.

PROCESS FOR THE PURIFICATION OF CANAGLIFLOZIN

The present invention provides a process for the preparation of (1S)-2,3,4,6-tetra- O-acetyl-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D- glucitol of Formula III. The invention also provides a process for the purification of canagliflozin using (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-5 thienyl]methyl]-4-methylphenyl]-D-glucitol of Formula III.

Synthesis of 2-arylmethyl-5-aryl-thiophene

The present invention provides a new synthetic process for the production of 2-arylmethyl-5-aryl-thiophene, an intermediate in the synthesis of C-aryl glycosides.

FAMILY OF ARYL, HETEROARYL, O-ARYL AND O-HETEROARYL CARBASUGARS

The present invention relates to a compound of the following formula (I): as well as its process of preparation, pharmaceutical and cosmetics composition comprising it and use thereof, notably as an inhibitor of the sodium-dependent glucose co-transporter, such as SGLTl, SGLT2 and SGLT3, in particular in the treatment or prevention of diabetes, and more particularly type-II diabetes, diabetes-related complications, such as arthritis of the lower extremities, cardiac infarction, renal insufficiency, neuropathy or blindness, hyperglycemia, hyperinsulinemia, obesity, hypertriglyceridemia, X syndrome and arteriosclerosis, as well as for its use as an anticancer, anti-infective, anti-viral, anti-thrombotic or anti- inflammatory drug, or for lightening, bleaching, depigmenting the skin, removing blemishes from the skin, particularly age spots and freckles, or preventing pigmentation of the skin.

Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus (1)

We discovered that C-glucosides 4 bearing a heteroaromatic ring formed metabolically more stable inhibitors for sodium-dependent glucose cotransporter 2 (SGLT2) than the O-glucoside, 2 (T-1095). A novel thiophene derivative 4b-3 (canagliflozin) was a highly potent and selective SGLT2 inhibitor and showed pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.

PROCESS FOR THE PREPARATION OF COMPOUNDS USEFUL AS INHIBITORS OF SGLT

The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.