Pioglitazone hydrochloride supplier

Name
[5-[[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-] thiazolidinedione hydrochloride
EINECS 629-731-9
CAS No. 112529-15-4
Article Data16
CAS DataBase
Density 1.26 g/cm³
Solubility soluble in N,N-dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in acetone and acetonitrile, practically insoluble in water, and insoluble in ether
Melting Point 193-194 ºC
Formula C₁₉H₂₁ClN₂O₃S
Boiling Point 575.4 ºC at 760 mmHg
Molecular Weight 392.906
Flash Point 301.8 ºC
Transport Information
Appearance white crystals or crystalline powder
Safety 22-24/25
Risk Codes 36/38
Molecular Structure
Hazard Symbols Xi
Synonyms (+-)-5-(p-(2-(5-Ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione monohydrochloride;Actos;2,4-Thiazolidinedione,5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-, monohydrochloride (9CI);2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-,monohydrochloride, (?à)-;5-[4-[2-(5-Ethyl-2-pyridyl)ethoxy]benzyl]thiazolidine-2,4-dionehydrochloride;Pioglitazone HCl;
PSA 93.59000
LogP 4.29040

Synthetic route

: 105355-27-9
Pioglitazone

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
With hydrogenchloride In ethanol at 10 - 65℃; for 4.25h; Product distribution / selectivity;	95%
With hydrogenchloride In ethanol; water at 10 - 65℃; for 4.25h; Product distribution / selectivity;	90%
With hydrogenchloride In methanol; water at 20℃; for 1h;	90.5%

: 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methylene]-thiazolidine-2,4-dione hydrogen chloride

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Stage #1: 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methylene]-thiazolidine-2,4-dione hydrogen chloride With hydrogen; palladium 10% on activated carbon In methanol; water at 50 - 60℃; under 3750.38 - 4500.45 Torr; for 15h; Stage #2: With hydrogenchloride In water at 0 - 5℃; for 3h;	84%

: 5223-06-3
5-ethyl-2-(2-hydroxyethyl)pyridine

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: 63 percent / NaH / dimethylformamide 2: H2 / 10percent Pd-C / methanol / 760 Torr / Ambient temperature 3: 1.)47percent HBr, NaNO2, 2.)Cu2O / 1.)MeOH, H2O, 5 deg C, 20 min., 2.)40 deg C 4: 53 percent / NaOAc / ethanol / Heating 5: 2N HCl / 6 h / Heating 6: 12.2 g / 11percent ethanolic HCl / 1 h / Ambient temperature View Scheme
Multi-step reaction with 10 steps 1: dihydrogen peroxide / acetic acid / 14 h / 100 °C 2: 0.5 h / 120 °C 3: sodium hydroxide / water / 2 h / 40 °C 4: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 5: N,N-dimethyl-formamide / 14 h / 80 °C 6: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 7: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 85 °C / Large scale 8: triethylamine / dichloromethane / 2 h / 0 °C 9: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 10: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 10 steps 1: dihydrogen peroxide / acetic acid / 14 h / 100 °C 2: 0.5 h / 120 °C 3: sodium hydroxide / water / 2 h / 40 °C 4: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 5: N,N-dimethyl-formamide / 14 h / 80 °C 6: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 7: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 85 °C / Large scale 8: triethylamine 9: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 10: hydrogenchloride / water; ethanol View Scheme

: 85583-40-0
4-[2-(5-ethylpyridin-2-yl)ethoxy]aniline

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.)47percent HBr, NaNO2, 2.)Cu2O / 1.)MeOH, H2O, 5 deg C, 20 min., 2.)40 deg C 2: 53 percent / NaOAc / ethanol / Heating 3: 2N HCl / 6 h / Heating 4: 12.2 g / 11percent ethanolic HCl / 1 h / Ambient temperature View Scheme

: 85583-54-6
4-(2-(5-ethyl-2-pyridyl)ethoxy)nitrobenzene

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: H2 / 10percent Pd-C / methanol / 760 Torr / Ambient temperature 2: 1.)47percent HBr, NaNO2, 2.)Cu2O / 1.)MeOH, H2O, 5 deg C, 20 min., 2.)40 deg C 3: 53 percent / NaOAc / ethanol / Heating 4: 2N HCl / 6 h / Heating 5: 12.2 g / 11percent ethanolic HCl / 1 h / Ambient temperature View Scheme

: 105355-25-7
methyl 2-bromo-3-{4-[2-(5-ethyl-pyridin-2-yl)ethoxy]phenyl}propionate

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: 53 percent / NaOAc / ethanol / Heating 2: 2N HCl / 6 h / Heating 3: 12.2 g / 11percent ethanolic HCl / 1 h / Ambient temperature View Scheme

: 105355-26-8
5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2-imino-4-thiazolidinone

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 2N HCl / 6 h / Heating 2: 12.2 g / 11percent ethanolic HCl / 1 h / Ambient temperature View Scheme
With hydrogenchloride; water for 15h; Product distribution / selectivity; Heating / reflux;
Stage #1: 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2-imino-4-thiazolidinone With methanol; oxalic acid In dichloromethane at 20℃; for 0.5h; Stage #2: With hydrogenchloride; water for 12h; Product distribution / selectivity; Heating / reflux;

: 350-46-9
4-Fluoronitrobenzene

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: 63 percent / NaH / dimethylformamide 2: H2 / 10percent Pd-C / methanol / 760 Torr / Ambient temperature 3: 1.)47percent HBr, NaNO2, 2.)Cu2O / 1.)MeOH, H2O, 5 deg C, 20 min., 2.)40 deg C 4: 53 percent / NaOAc / ethanol / Heating 5: 2N HCl / 6 h / Heating 6: 12.2 g / 11percent ethanolic HCl / 1 h / Ambient temperature View Scheme

: 674798-32-4
2-bromo-3-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}propionic acid

: 17356-08-0
thiourea

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Stage #1: 2-bromo-3-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}propionic acid; thiourea With sodium acetate In ethanol for 3h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol; water for 18h; Heating / reflux; Stage #3: With ammonia In ethanol; water at 20℃;

: 1034515-30-4
5-{4-[2-(5-ethyl-pyridin-2-yl)ethoxy]-benzyl}-2-morpholin-4-yl-thiazol-4-one

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
With hydrogenchloride; water; isopropyl alcohol for 8h; Product distribution / selectivity; Heating / reflux;

: 1034515-42-8
N-(5-{4-[2-(5-ethyl-pyridin-2-yl)-ethoxy]-benzyl}-4-oxo-4,5-dihydrothiazol-2-yl)-methanesulfonamide

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
With hydrogenchloride; water for 3h; Product distribution / selectivity; Heating / reflux;

: 1034515-24-6
N-(5-{4-[2-(5-ethyl-pyridin-2-yl)ethoxy]benzyl}-4-oxo-4,5-dihydrothiazol-2-yl)-4-methylbenzenesulfonamide

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Stage #1: N-(5-{4-[2-(5-ethyl-pyridin-2-yl)ethoxy]benzyl}-4-oxo-4,5-dihydrothiazol-2-yl)-4-methylbenzenesulfonamide With hydrogenchloride; water for 8h; Heating / reflux; Stage #2: With hydrogenchloride In ethyl acetate at 25 - 30℃; for 2h; Product distribution / selectivity;

: 144809-28-9
5-{4-[2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Stage #1: 5-{4-[2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione With sodium tetrahydroborate; cobalt(II) nitrate hexahydrate; butane-2,3-dione dioxime; sodium hydroxide In water; N,N-dimethyl-formamide at 35℃; for 6h; Large scale reaction; Stage #2: With acetic acid In water; N,N-dimethyl-formamide at 25℃; for 0.75h; pH=6.5 - 7; Large scale reaction; Stage #3: With hydrogenchloride In water; isopropyl alcohol at 25 - 80℃; Large scale reaction;	49.6 kg
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; hydrogen / methanol / 16 h / 3102.97 Torr 2: hydrogenchloride / water; ethanol View Scheme

Yield

Stage #1: 5-{4-[2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione With sodium tetrahydroborate; cobalt(II) nitrate hexahydrate; butane-2,3-dione dioxime; sodium hydroxide In water; N,N-dimethyl-formamide at 35℃; for 6h; Large scale reaction;
Stage #2: With acetic acid In water; N,N-dimethyl-formamide at 25℃; for 0.75h; pH=6.5 - 7; Large scale reaction;
Stage #3: With hydrogenchloride In water; isopropyl alcohol at 25 - 80℃; Large scale reaction;

49.6 kg

Multi-step reaction with 2 steps
1: palladium 10% on activated carbon; hydrogen / methanol / 16 h / 3102.97 Torr
2: hydrogenchloride / water; ethanol
View Scheme

: 646519-90-6
5-{4-[2-(5-ethylpyridin-2-yl)-2-mesylethoxy]benzylidene}-2,4-thiazolidene dione

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 2: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 3102.97 Torr 2: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 3: hydrogenchloride / water; ethanol View Scheme

: 5-{4-[2-(5-ethylpyridin-2-yl)-2-mesylethoxy]benzyl}-2,4-thiazolidene dione

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 2: hydrogenchloride / water; ethanol View Scheme

: 646519-92-8
5-{4-[2-(5-ethylpyridin-2-yl)-2-tosylethoxy]benzylidene}-2,4-thiazolidene dione

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 2: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 2: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 2: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 3: hydrogenchloride / water; ethanol View Scheme

: 5-{4-[2-(5-ethylpyridin-2-yl)-2-tosylethoxy]benzyl}-2,4-thiazolidene dione

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 2: hydrogenchloride / water; ethanol View Scheme

: 646519-94-0
5-{4-[2-chloro-2-(5-ethylpyridn-2-yl)ethoxy]benzylidene}-2,4-thiazolidene dione

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / tetrahydrofuran / 12 h 2: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 70 °C 2: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 3 steps 1: zinc; acetic acid / methanol / 15 h / 25 - 30 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 16 h / 3102.97 Torr 3: hydrogenchloride / water; ethanol View Scheme

: 90643-32-6
2-(5-ethyl-1-oxypyridin-2-yl)ethanol

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 10 steps 1: 0.5 h / 120 °C 2: sodium hydroxide / water / 2 h / 40 °C 3: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 4: N,N-dimethyl-formamide / 14 h / 80 °C 5: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 6: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 85 °C / Large scale 7: thionyl chloride / chloroform / 2 h / Reflux 8: hydrogenchloride 9: zinc; propionic acid / ethanol / 12 h 10: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 10 steps 1: 0.5 h / 120 °C 2: sodium hydroxide / water / 2 h / 40 °C 3: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 4: N,N-dimethyl-formamide / 14 h / 80 °C 5: thionyl chloride / chloroform / 1 h / Reflux 6: acetic acid; piperidine / toluene / Heating 7: hydrogen / tetrahydrofuran / 12 h 8: hydrogenchloride 9: zinc; propionic acid / ethanol / 12 h 10: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 10 steps 1: 0.5 h / 120 °C 2: sodium hydroxide / water / 2 h / 40 °C 3: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 4: N,N-dimethyl-formamide / 14 h / 80 °C 5: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 6: thionyl chloride / chloroform / 3 h / Reflux 7: hydrogen / tetrahydrofuran / 12 h 8: hydrogenchloride 9: zinc; propionic acid / ethanol / 12 h 10: hydrogenchloride / water; ethanol View Scheme

: 1-(5-ethylpyridin-2-yl)ethan-1,2-diol

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 2: N,N-dimethyl-formamide / 14 h / 80 °C 3: thionyl chloride / chloroform / 1 h / Reflux 4: acetic acid; piperidine / toluene / Heating 5: hydrogen / tetrahydrofuran / 12 h 6: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 6 steps 1: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 2: N,N-dimethyl-formamide / 14 h / 80 °C 3: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 4: thionyl chloride / chloroform / 3 h / Reflux 5: hydrogen / tetrahydrofuran / 12 h 6: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 6 steps 1: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 2: N,N-dimethyl-formamide / 14 h / 80 °C 3: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 4: triethylamine / dichloromethane / 2 h / 0 °C 5: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 6: hydrogenchloride / water; ethanol View Scheme

: 5-ethyl-2-[2-oxo-(1,3,2)dioxathiolan-4-yl]pyridine

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 14 h / 80 °C 2: thionyl chloride / chloroform / 1 h / Reflux 3: acetic acid; piperidine / toluene / Heating 4: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 70 °C 5: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 14 h / 80 °C 2: triethylamine / dichloromethane / 4 h / 0 - 5 °C 3: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 4: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 5: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 14 h / 80 °C 2: triethylamine / dichloromethane / 4 h / 0 - 5 °C 3: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 4: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 5: hydrogenchloride / water; ethanol View Scheme

: 4-[2-chloro-2-(5-ethyl-2-pyridyl)ethoxy]benzaldehyde

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 10 steps 1.1: acetic acid; piperidine / toluene / Heating 2.1: hydrogen / tetrahydrofuran / 12 h 3.1: zinc; acetic acid / 15 h / 25 - 30 °C 4.1: water; N-Bromosuccinimide / tert-butyl alcohol / 1.17 h / 25 - 30 °C 5.1: potassium carbonate / tert-butyl alcohol / 1.17 h / Reflux 5.2: 11 h / Reflux 6.1: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 7.1: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 85 °C / Large scale 8.1: triethylamine 9.1: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 10.1: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 10 steps 1.1: acetic acid; piperidine / toluene / Heating 2.1: hydrogen / tetrahydrofuran / 12 h 3.1: zinc; acetic acid / 15 h / 25 - 30 °C 4.1: water; N-Bromosuccinimide / dimethyl sulfoxide / 0.5 h / -5 - 0 °C 5.1: potassium carbonate / tert-butyl alcohol / 1.17 h / Reflux 5.2: 11 h / Reflux 6.1: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 7.1: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 85 °C / Large scale 8.1: triethylamine 9.1: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 10.1: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 10 steps 1.1: acetic acid; piperidine / toluene / Heating 2.1: hydrogen / tetrahydrofuran / 12 h 3.1: zinc; acetic acid / 15 h / 25 - 30 °C 4.1: water; N-Bromosuccinimide / dimethyl sulfoxide / 0.5 h / -5 - 0 °C 5.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.08 h 5.2: 15 h / 25 - 90 °C 6.1: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 7.1: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 85 °C / Large scale 8.1: triethylamine 9.1: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 10.1: hydrogenchloride / water; ethanol View Scheme

: 4-[2-(5-ethylpyridin-2-yl)-2-mesylethoxy]benzaldehyde

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 2: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 3: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 4 steps 1: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 14 h / 3102.97 Torr 3: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 4: hydrogenchloride / water; ethanol View Scheme

: 4-[2-(5-ethylpyridn-2-yl)-2-tosylethoxy]benzaldehyde

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 2: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 3: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 3 steps 1: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 2: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 3: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 4 steps 1: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 2: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 3: acetic acid; sodium tetrahydroborate / 15 h / 40 - 45 °C 4: hydrogenchloride / water; ethanol View Scheme

: 646519-89-3
5-{4-[2-chloro-2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-2,4-thiazolidene dione hydrochloride

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc; propionic acid / ethanol / 12 h 2: hydrogenchloride / water; ethanol View Scheme

: 123-08-0
4-hydroxy-benzaldehyde

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / tert-butyl alcohol; water / 1.5 h / 25 °C / Large scale 1.2: 0.75 h / Large scale 1.3: PEG 4000 / 17 h / 78 °C / Large scale 2.1: thionyl chloride / chloroform / 1 h / Reflux 3.1: acetic acid; piperidine / toluene / Heating 4.1: hydrogen / tetrahydrofuran / 12 h 5.1: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / tert-butyl alcohol; water / 1.5 h / 25 °C / Large scale 1.2: 0.75 h / Large scale 1.3: PEG 4000 / 17 h / 78 °C / Large scale 2.1: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 3.1: triethylamine / dichloromethane / 2 h / 0 °C 4.1: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 5.1: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.08 h 1.2: 15 h / 25 - 90 °C 2.1: thionyl chloride / chloroform / 1 h / Reflux 3.1: acetic acid; piperidine / toluene / Heating 4.1: hydrogen / tetrahydrofuran / 12 h 5.1: hydrogenchloride / water; ethanol View Scheme

: 471295-98-4
4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]benzaldehyde

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / chloroform / 1 h / Reflux 2: acetic acid; piperidine / toluene / Heating 3: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 70 °C 4: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 4 steps 1: thionyl chloride / chloroform / 1 h / Reflux 2: acetic acid; piperidine / toluene / Heating 3: hydrogen / tetrahydrofuran / 12 h 4: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 4 h / 0 - 5 °C 2: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 3: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 3 h / 60 - 65 °C 4: hydrogenchloride / water; ethanol View Scheme

: acetic acid 2-acetoxy-2-(5-ethyl-1-pyridin-2-yl)ethyl ester

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1: sodium hydroxide / water / 2 h / 40 °C 2: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 3: N,N-dimethyl-formamide / 14 h / 80 °C 4: thionyl chloride / chloroform / 1 h / Reflux 5: acetic acid; piperidine / toluene / Heating 6: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 70 °C 7: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 7 steps 1: sodium hydroxide / water / 2 h / 40 °C 2: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 3: N,N-dimethyl-formamide / 14 h / 80 °C 4: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 5: thionyl chloride / chloroform / 3 h / Reflux 6: sodium tetrahydroborate; butane-2,3-dione dioxime; cobalt(II) chloride hexahydrate / water; N,N-dimethyl-formamide / 4 h / 65 - 70 °C 7: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 7 steps 1: sodium hydroxide / water / 2 h / 40 °C 2: thionyl chloride; triethylamine / dichloromethane / 1.25 h / 0 - 5 °C 3: N,N-dimethyl-formamide / 14 h / 80 °C 4: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 5: triethylamine / dichloromethane / 2 h / 0 °C 6: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 7: hydrogenchloride / water; ethanol View Scheme

: 5408-74-2
5-ethyl-2-vinyl-pyridine

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / tert-butyl alcohol; water / 1.5 h / 25 °C / Large scale 1.2: 0.75 h / Large scale 1.3: PEG 4000 / 17 h / 78 °C / Large scale 2.1: thionyl chloride / chloroform / 1 h / Reflux 3.1: acetic acid; piperidine / toluene / Heating 4.1: hydrogen / tetrahydrofuran / 12 h 5.1: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / tert-butyl alcohol; water / 1.5 h / 25 °C / Large scale 1.2: 0.75 h / Large scale 1.3: PEG 4000 / 17 h / 78 °C / Large scale 2.1: pyrrolidine / methanol / 2 h / 50 - 55 °C / Large scale 3.1: triethylamine / dichloromethane / 2 h / 0 °C 4.1: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 5.1: hydrogenchloride / water; ethanol View Scheme
Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / tert-butyl alcohol; water / 1.5 h / 25 °C / Large scale 1.2: 0.75 h / Large scale 1.3: PEG 4000 / 17 h / 78 °C / Large scale 2.1: triethylamine / dichloromethane / 4 h / 0 - 5 °C 3.1: acetic acid; piperidine / toluene / 4 h / 120 - 130 °C 4.1: palladium 10% on activated carbon; hydrogen / water; methanol / 14 h / 3102.97 Torr 5.1: hydrogenchloride / water; ethanol View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 1134163-24-8
rac-5-({p-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl}methyl)-(5-2H)-1,3-thiazolidine-2,4-dione

Conditions

Conditions	Yield
With triethylamine In dimethylsulfoxide-d6; d(4)-methanol at 20℃; for 108h;	95%
With dimethylsulfoxide-d6; d(4)-methanol; triethylamine at 20℃; for 108h;	95%
With dimethylsulfoxide-d6; d(4)-methanol; triethylamine at 20℃; for 108h;	95%

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 21085-72-3
1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester

: 1296832-69-3
3-((2R,3R,4S,5S,6S)-3,4,5-triacetoxy-6-methoxycarbonyl-tetrahydropyran-2-yl)-5-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]benzyl}-thiazolidine-2,4-dione

Conditions

Conditions	Yield
With caesium carbonate In acetonitrile at 70℃; for 3h;	83%

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 657-24-9
dimethylbiguanide

: metformin (RS)-5-(4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl)thiazolidine-2,4-dioxothiazolidin-3-ide

Conditions

Conditions	Yield
In water	64%

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 7646-85-7
zinc(II) chloride

: C38H38N4O6S2Zn(2+)*2Cl(1-)

Conditions

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide at 70℃; pH=6 - 6.5;	51.08%

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 1296832-75-1
3-((2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydropyran-2-yl)-5-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]benzyl}-thiazolidine-2,4-dione

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: caesium carbonate / acetonitrile / 3 h / 70 °C 2: hydrogenchloride / 1,4-dioxane / 76 h / 20 °C 3: morpholine; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 4 h / 20 °C View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 1296832-76-2
(2S,3S,4S,5R,6R)-6-(1-carboxy-2-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl}-ethylsulfanylcarbonylamino)-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: caesium carbonate / acetonitrile / 3 h / 70 °C 2: hydrogenchloride / 1,4-dioxane / 76 h / 20 °C 3: morpholine; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 4 h / 20 °C 4: water; acetonitrile 5: sodium acetate / water; acetonitrile / 296 h / 20 °C View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 1296832-72-8
3-((2R,3R,4S,5S,6S)-6-allyloxycarbonyl-3,4,5-trihydroxy-tetrahydropyran-2-yl)-5-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]benzyl}-thiazolidine-2,4-dione

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate / acetonitrile / 3 h / 70 °C 2: hydrogenchloride / 1,4-dioxane / 76 h / 20 °C View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 3-((2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydropyran-2-yl)-5-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]benzyl}-thiazolidine-2,4-dione trifluoroacetate

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: caesium carbonate / acetonitrile / 3 h / 70 °C 2: hydrogenchloride / 1,4-dioxane / 76 h / 20 °C 3: morpholine; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 4 h / 20 °C 4: water; acetonitrile View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: (2S,3S,4S,5R,6R)-6-(1-carboxy-2-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl}-ethylsulfanylcarbonylamino)-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid trifluoroacetate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: caesium carbonate / acetonitrile / 3 h / 70 °C 2: hydrogenchloride / 1,4-dioxane / 76 h / 20 °C 3: morpholine; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 4 h / 20 °C 4: water; acetonitrile 5: sodium acetate / water; acetonitrile / 296 h / 20 °C 6: water; acetonitrile View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 1263978-84-2
(5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: water; methanol / 96 h / Inert atmosphere 2.1: tetrahydrofuran / 1.5 h / 20 - 35 °C / Inert atmosphere 2.2: 20 °C / Reflux; Inert atmosphere View Scheme

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 1263978-86-4
(5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione tosylate

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: water; methanol / 96 h / Inert atmosphere 2: isopropyl alcohol / 0.5 h / 20 - 40 °C / Inert atmosphere View Scheme

: 87-69-4
L-Tartaric acid

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

A: 1263978-84-2
(5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate

B: C4H6O6*C19H20N2O3S

Conditions

Conditions	Yield
In methanol; water for 96h; Inert atmosphere;	A n/a B n/a

...Expand

: 32634-66-5
Di-p-toluoyl-L-tartaric acid

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

A: (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione (-)-O,O'-di-p-toluoyl-L-tartrate

B: C19H20N2O3S*C20H18O8

Conditions

Conditions	Yield
In methanol; water for 96h; Inert atmosphere;	A n/a B n/a

...Expand

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 2743-38-6
O,O'-dibenzoyl-L-tartaric acid

A: (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione (-)-O,O'-dibenzoyl-L-tartrate

B: (x)C18H14O8*C19H20N2O3S

Conditions

Conditions	Yield
In methanol; water for 96h; Product distribution / selectivity; Inert atmosphere;	A n/a B n/a

...Expand

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

A: 1229114-66-2
3-(4-(2-(5-ethylpyridine-2yl)ethoxy)phenyl)-2-mercaptopropanoic acid

B: 1229114-67-3
2-(1-carboxy-2-{4-[2-(5-ethylpyridine-2yl)-ethoxy]phenyl}-ethyldisulfanyl)-3-{4-[2-(5-ethylpyridine-2yl)-ethoxy]phenyl}propanoic acid

Conditions

Conditions	Yield
With sodium hydroxide at 80℃; for 24h;

: 112529-15-4
5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride

: 145350-09-0
rac-2-(2-{4-[(2,4-dioxothiazolidin-5-yl)methyl]phenoxy}ethyl)-5-ethylpyridine-1-oxide

Conditions

Conditions	Yield
With dihydrogen peroxide at 60 - 80℃; for 24h;

Pioglitazone hydrochloride Chemical Properties

IUPAC Name: 5-[[4-[2-(5-Ethylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione hydrochloride
Molecular Formula: C₁₉H₂₁ClN₂O₃S
Molecular Weight: 392.90 g/mol
Canonical SMILES: CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3.Cl
InChI: InChI=1/C19H20N2O3S.ClH/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17;/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23);1H
Classification Code: Antidiabetic
Product Categories: Active Pharmaceutical Ingredients; Antidiabetic; Diabetes; Heterocycles; Intermediates & Fine Chemicals; Pharmaceuticals; Sulfur & Selenium Compounds;API's; Pioglitazone
H-Bond Donor: 2
H-Bond Acceptor: 4
Rotatable Bond Count: 7
Tautomer Count: 10
Exact Mass: 392.096141
MonoIsotopic Mass: 392.096141
Topological Polar Surface Area: 68.3
Heavy Atom Count: 26
Complexity: 466
Melting Point: 193-194 °C
Flash Point: 301.8 °C
Enthalpy of Vaporization: 86.19 kJ/mol
Boiling Point: 575.4 °C at 760 mmHg
Vapour Pressure of Pioglitazone HCl (CAS NO.112529-15-4): 3.03E-13 mmHg at 25 °C

Pioglitazone hydrochloride Uses

Pioglitazone HCl (CAS NO.112529-15-4) is used as an antidiabetic.

Pioglitazone hydrochloride Safety Profile

Hazard Codes: Irritant Xi
Risk Statements: 36/38
R36/38: Irritating to eyes and skin.
Safety Statements of Pioglitazone HCl (CAS NO.112529-15-4): 22-24/25
S22: Do not breathe dust.
S24/25: Avoid contact with skin and eyes.

Pioglitazone hydrochloride Specification

Pioglitazone HCl (CAS NO.112529-15-4), its Synonyms are 2,4-Thiazolidinedione, 5-((4-(2-(5-ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-, monohydrochloride, (+-)- ; (+-)-5-(p-(2-(5-Ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione monohydrochloride ; Pioglitazone hydrochloride ; Actos . It is colourless prisms.

Product Name

[5-[[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-] thiazolidinedione hydrochloride

Synthetic route

Pioglitazone hydrochloride Chemical Properties

Pioglitazone hydrochloride Uses

Pioglitazone hydrochloride Safety Profile

Pioglitazone hydrochloride Specification

Related Products

Hot Products