7-BROMO-5-FLUOROINDOLE

7-BROMO-5-FLUOROINDOLE Property

Melting point:

20-25°C

Boiling point:

315.1±22.0 °C(Predicted)

Density 

1.750±0.06 g/cm3(Predicted)

Flash point:

>110℃

storage temp. 

2-8°C

pka

14.49±0.30(Predicted)

form 

solid

Appearance

Off-white to light brown <20°C Solid,>25°C Liquid

Sensitive 

Light Sensitive

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

22-37/38-41

Safety Statements 

26-36/37/39

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H318Causes serious eye damage

H335May cause respiratory irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

7-BROMO-5-FLUOROINDOLE Chemical Properties,Usage,Production

Uses

7-Bromo-5-fluoroindole is an HIV-1 attachment inhibitor.

Synthesis

(a) Synthesis of 5-fluoro-7-bromoindole. 2-Bromo-4-fluoroaniline (13.8 g, 72.6 mmol) was slowly added dropwise to a dichloromethane solution of boron trichloride (1.0 M, 81.1 mL, 81.1 mmol) cooled in ice water. The reaction mixture was gradually warmed to room temperature with continuous stirring for 30 minutes. Subsequently, chloroacetonitrile (13.5 mL, 87.1 mmol), aluminum chloride (13.5 g, 98.4 mmol) and 1,2-dichloroethane (95 mL) were added sequentially. The reaction system was heated to 70 °C to evaporate the dichloromethane, followed by refluxing the reaction for 24 hours. Upon completion of the reaction, it was cooled to 0-5 °C, 2.5 M HCl (130 mL) was carefully added and heated to 80 °C and kept at 80 °C for 1 h until the solid was completely dissolved. The aqueous layer was separated and the organic phase was extracted with dichloromethane. The organic layers were combined, washed sequentially with water and brine, dried over anhydrous sodium sulfate and concentrated to give a yellow solid (11 g, 56.9% yield), which could be used directly in the next reaction. The crude was dissolved in a solvent mixture of dioxane (68 mL) and water (7.6 mL) and sodium borohydride (1.64 g) was added in batches. The reaction was carried out at room temperature for 30 minutes to confirm complete consumption of the raw material and then heated to reflux for 18 hours. The reaction solution was cooled to room temperature, treated sequentially with 0.1 N HCl (70 mL), 2 N HCl (20 mL) and concentrated HCl (15 mL) and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 5-fluoro-7-bromoindole (4.4 g, 52.2% yield).1H NMR (400 MHz, CDCl3) δ 6.49 (dd, J = 2.35, 3.13 Hz, 1H), 7.06 (d, J = 2.35, 8.60 Hz, 1H), 7.14- 7.17 (m, 2H), 8.18 (br, 1H); MS (ES, m/z): C8H5BrFN [M+] calcd for 79Br: 211.9, found: 211.9; calcd for 81Br: 214.0, found: 214.0.

References

[1] Patent: US2004/48915, 2004, A1