122320-74-5

Basic information

• Product Name: 5-[4-[2-[N-Methyl-N-(2-pyridinyl)amino]ethoxy]benzylidene]-2,4-thiazolidinedione
• Synonyms: 5-[(4-{2-[Methyl(pyridin-2-yl)aMino]ethoxy}phenyl)Methylidene]-1,3-thiazolidine-2,4-dione;5-{4-[2-(N-Methyl-2-pyridyl)aMino]ethoxy}benzylidene}-2,4-thiazolidinedione;5-[[4-[2-[Methyl(pyridin-2-yl)amino]ethoxy]phenyl]methylene] -1,3-thiazolidine- 2,4-dione;5-[4-[N-(Methyl-2-Pyridinylamino)Ethyl]Benylidene]-2,4-Thiazolid-Inedione;5-[4-[2-(N-Methyl-N-2-Pyridyl)Aminoethoxy]Benzyl]-2-Imino-4-Thizaolidinone;(5-(4-(2-(N-Methyl-N-(2-pyridinyl)amino)ethoxy)benzylidene)-2,4-thiazolidinedione;5-{4-[2-(Methyl-2-pyridinylamino)-ethoxy]-phenyl}-methylene}-2,4-thiazolidinedio;5-[4-[N-(METHYL-2-PYRIDINYLAMINO)ETHOXY]BENZYLIDENE-2,4-
• CAS NO: 122320-74-5
• Molecular Formula: C₁₈H₁₇N₃O₃S
• Molecular Weight: 355.41
• EINECS: 1806241-263-5
• Mol File: 122320-74-5.mol
• Article Data: 5

Chemical Properties

• Appearance: Yellow crystalline powder
• Density: 1.361 g/cm³
• Refractive Index: 1.688
• Storage Temp.: 2-8°C
• PKA: 7.26±0.20(Predicted)
• CAS DataBase Reference: 5-[4-[2-[N-Methyl-N-(2-pyridinyl)amino]ethoxy]benzylidene]-2,4-thiazolidinedione(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[4-[2-[N-Methyl-N-(2-pyridinyl)amino]ethoxy]benzylidene]-2,4-thiazolidinedione(122320-74-5)
• EPA Substance Registry System: 5-[4-[2-[N-Methyl-N-(2-pyridinyl)amino]ethoxy]benzylidene]-2,4-thiazolidinedione(122320-74-5)

Safety Data

• Hazardous Substances Data: 122320-74-5(Hazardous Substances Data)

Usage

Uses

(5E)-Rosiglitazone is the E-isomer of Rosiglitazone (R693505). Rosiglitazone is an insulin sensitizer; binds to peroxisome proliferator activated receptor gamma (PPAR- γ).

InChI:InChI=1/C18H17N3O3S/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15/h2-9,12H,10-11H2,1H3,(H,20,22,23)/b15-12-

Synthetic route

2,4-thiazolidinedion (2295-31-0) + 4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzaldehyde (122321-03-3) → 5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5)

Conditions	Yield
With pyrrolidine; acetic acid In toluene for 3h; Heating; Reflux;	95%
In toluene for 5h; Reflux;	95.3%
piperdinium acetate In toluene for 5h; Heating / reflux;

2-(N-methyl-N-(pyridin-2-yl)amino)ethanol (122321-04-4) + 5-(4-fluorobenzylidene)-1,3-thiazolidine-2,4-dione → 5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 100℃; for 4h;	80%

C9H6FNO → 5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: C9H14N2OS / dimethyl sulfoxide / 48 h / 600 °C / 7500.75 Torr 2: potassium hydroxide / dimethyl sulfoxide / 4 h / 100 °C View Scheme

2-chloropyridine (109-09-1) → 5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: triphenylmethyl sodium / 8 h / 70 °C 2: potassium hexamethylsilazane / 1 h / 60 °C 3: toluene / 5 h / Reflux View Scheme

2-(N-methyl-N-(pyridin-2-yl)amino)ethanol (122321-04-4) → 5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hexamethylsilazane / 1 h / 60 °C 2: toluene / 5 h / Reflux View Scheme

5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5) → rosiglitazone (122320-73-4)

Conditions	Yield
With BuMnCl In methanol at 20℃; for 0.5h;	93.7%
With iodine; magnesium In methanol for 3h; Reflux;	92%
With pyridine; lithium borohydride In tetrahydrofuran; water	77%

5-{4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]benzylidene}thiazolin-2,4-dione (122320-74-5) + L-Selectride → rosiglitazone (122320-73-4)

Conditions	Yield
With hydrogenchloride; sodium hydroxide; dihydrogen peroxide In tetrahydrofuran

Upstream product

• 122321-04-4 2-(N-methyl-N-(pyridin-2-yl)amino)ethanol 
• 109-09-1 2-chloropyridine 
• 2295-31-0 thiazoline-2,4-dione 
• 122321-03-3 4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzaldehyde 

Downstream Products

• 122320-73-4 rosiglitazone 

Relevant articles and documents

Preparation method of rosiglitazone

The invention provides a preparation method of rosiglitazone. The preparation method is characterized by comprising the following steps: reacting 2-chloropyridine with 2-methylaminoethanol under the catalysis of sodium triphenylmethyl to generate 2-[N-methyl-N-(2-pyridine) amino] ethanol; then carrying out Williamson synthesis reaction on the 2-[N-methyl-N-(2-pyridine) amino] ethanol and 4-fluorobenzaldehyde under the catalysis of bis (trimethylsilyl) amino potassium to obtain 4-[2-[N-methyl-N-(2-pyridine) amino] ethoxy] benzaldehyde; then carrying out condensation reaction with thiazoline-2,4-diketone to obtain 5-{4-[2-[N-methyl-N-(2-pyridine) amino] ethoxy] benzylidene} thiazoline-2, 4-diketone; and carrying out reduction reaction under the catalysis of an organic manganese reagent to obtain the rosiglitazone. The preparation method is simple, mild in condition, high in reaction yield and suitable for industrial production.

Process for the Preparation of Intermediates of Rosiglitazone, Rosiglitazone and New Polymorphic Forms Thereof

The invention relates to a polymorphic form of 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene)-2,4-thiazolidinedione (Formula (I)): to a process for its preparation and to the use of such compound for preparing rosiglitazone in the form of a free base or a salt thereof. The invention also relates to a polymorphic form of rosiglitazone in the form of a free base, to a process for its preparation and to the use of such polymorph for preparing a salt of rosiglitazone. The invention also relates to a process of preparing a polymorphic form of a rosiglitazone salt.

COMPOUNDS

Compounds of formula (I) or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine