928672-86-0

Basic information

• Product Name: Canagliflozin heMihydrate
• Synonyms: Cagliflozin heMihydrate;Canagliflozin hydrate (2:1);Canagliflozin heMihydrate;D-Glucitol, 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]Methyl]-4-Methylphenyl]-, hydrate (2:1);Canagliflozin heMihydrates;(1S)-1,5-Anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hydrate (2:1);(2S,3R,4R,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol Hemihydrate
• CAS NO: 928672-86-0
• Molecular Formula: 2(C24H25FO5S).H2O
• Molecular Weight: 907.05
• EINECS: 202-303-5
• Product Categories: Canagliflozin
• Mol File: 928672-86-0.mol

Chemical Properties

• Appearance: Light Yellow Solid
• Density: 99
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: Canagliflozin heMihydrate(CAS DataBase Reference)
• NIST Chemistry Reference: Canagliflozin heMihydrate(928672-86-0)
• EPA Substance Registry System: Canagliflozin heMihydrate(928672-86-0)

Safety Data

• Hazardous Substances Data: 928672-86-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Canagliflozin hemihydrate is used as an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus (T2DM) and obesity. It helps in reducing the renal threshold for glucose excretion and increasing urinary glucose excretion, thereby lowering plasma glucose and HbA1c levels. Its safety in combination with other antidiabetic agents and its effect on body weight reduction make it a promising candidate for managing T2DM and obesity.

Synthesis

Synthesis of the aglycone region of canagliflozin was described in a separate patent by first condensing commercially available 5- bromo-2-methylbenzoyl chloride (14) and 2-(4-fluorophenyl)- thiophene (15) under Friedel–Crafts acylation conditions to give ketone 16 in 69% yield as a crystalline solid. Ketone 16 was then reduced with triethylsilyl hydride in the presence of BF3Et2O at low temperature to give aglycone bromide 17 in 70% yield. The precursor for the glycoside moiety, commercially available glycoside triol 18, was selectively treated with t-butyldiphenylsilyl chloride (TBDPSCl) in THF in the presence of imidazole to give the bis-silyl ether 19 in 81% yield. Next, a unique, stereospecific b-C-arylglucosidation was developed to secure the union of the aglyone- and glycoside-containing portions of canagliflozin. Bromide 17 was subjected to magnesium powder under standard Grignard conditions prior to treatment with AlCl3 in THF in situ. This resulting mixture was then exposed to a solution of compound 19 in PhOMe which had been pre-treated with n-BuLi, and the entire mixture was then warmed to 150 ℃ for 5 h to ultimately give the b-anomer 20 in 56% yield. Finally, removal of the silyl groups within 20 with tetrabutyl ammonium fluoride (TBAF) in THF delivered canagliflozin hydrate (III) in 73% yield.

Upstream product

• 842133-18-0 canagliflozin 
• 1030825-21-8 methyl 1-C-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methyl-phenyl)-D-glucopyranoside 

Relevant articles and documents

NOVEL CRYSTALLINE HYDRATES OF 1-(?-D-GLUCOPYRANOSYL)-4-METHYL-3-[5-(4-FLUOROPHENYL)-2-THIENYLMETHYL]BENZENE

The present invention relates to non-stoichiometric crystalline hydrates of 1-(?-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, processes for their preparation, and their use as medicaments. In addition the present invention relates to pharmaceutical compositions comprising an effective amount of the novel crystalline hydrates.

Crystalline form of 1-(beta-D-glucopyransoyl)-4-methyl-3-[5-(4-fluorophenyl)-2- thienylmethyl]benzene hemihydrate

A novel crystal form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate, and having favorable characteristics, is characterized by its x-ray powder diffraction pattern and/or by its infra-red spectrum.