2-(4-BroMopyridin-2-yl)propan-2-ol

2-(4-BroMopyridin-2-yl)propan-2-ol Property

Boiling point:

269.9±25.0 °C(Predicted)

Density 

1.474±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

13.23±0.29(Predicted)

form 

solid

color 

White

Safety

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

2-(4-BroMopyridin-2-yl)propan-2-ol Chemical Properties,Usage,Production

Uses

2-(4-Bromopyridin-2-yl)propan-2-ol is used in preparation of pyrazolo[1,5-a]pyridine-derivatives as TGF-beta receptor inhibitor for prevention/treatment of TGF-betaR1(ALK5)-mediated diseases.

Synthesis

1. Assemble a 3 L three-necked round-bottomed flask equipped with a dropping funnel, reflux condenser, nitrogen inlet, and temperature probe. 2. Add methylmagnesium bromide (3.2 M, dissolved in 2-methyltetrahydrofuran, 239.07 mL, 765.01 mmol) to the flask and cool to 0°C in an ice bath. 3. A solution of ethyl 4-bromopyridine-2-carboxylate (80.0 g, 347.73 mmol) in tetrahydrofuran (THF, 800.0 mL) was added to a dropping funnel. 4. The THF solution of ethyl 4-bromopyridine-2-carboxylate was slowly added dropwise to a solution of methylmagnesium bromide, with the dropwise acceleration being controlled to keep the reaction temperature below 25°C. The reaction was completed with the addition of ethyl 4-bromopyridine-2-carboxylate (80.0 g, 347.73 mmol). 5. After the dropwise addition is complete, the ice bath is removed and the reaction mixture is stirred at 25°C for 30 minutes. 6. The reaction mixture was cooled to 5°C and a 1 M aqueous hydrochloric acid solution was slowly added dropwise, with controlled drop acceleration to maintain the internal temperature below 30°C, until the pH of the reaction mixture was neutral. 7. The organic layer was separated by diluting the reaction mixture with ethyl acetate (EtOAc, 200 mL). 8. The organic layer was dried with anhydrous sodium sulfate, filtered through a CELITE? plug and washed with EtOAc. 9. The filtrate was concentrated to give an orange colored oil. 10. Purification by silica gel column chromatography using hexane/EtOAc (3:1) as eluent gave 2-(4-bromopyridin-2-yl)-2-propanol (63.15 g, 84.0% yield) as a colorless oil. 11. Mass spectrometry (MS) analysis showed m/z: 216/218 ([M+1]/[M+3]).

References

[1] Patent: US2016/96823, 2016, A1. Location in patent: Paragraph 0040