5-CHLOROISOQUINOLINE

5-CHLOROISOQUINOLINE Property

Melting point:

69-73 °C

storage temp. 

Sealed in dry,Room Temperature

solubility 

Chloroform (Slightly), Ethyl Acetate (Slightly)

form 

Solid

color 

White

CAS DataBase Reference

5430-45-5(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

22-41

Safety Statements 

26-39

RIDADR 

UN 2811

WGK Germany 

3

HazardClass 

6.1

PackingGroup 

Ⅲ

HS Code 

2933499090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H318Causes serious eye damage

Precautionary statements

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

5-CHLOROISOQUINOLINE Chemical Properties,Usage,Production

Chemical Properties

White Solid

Uses

5-Chloroisoquinoline (compound 42) is an inhibitor of SARM1 (Sterile alpha and toll/interleukin receptor (TIR) motif containing protein 1), an enzyme involved in axon degeneration that catalyzes multiple activities through a ternary complex mechanism. 5-Chloroisoquinoline can be used in the study of neurodegenerative diseases or axon degeneration[1].

Synthesis

Isoquinoline (1; 12.9 g, 0.1 mol, 1.0 equiv) was slowly added to concentrated H2SO4 (100 mL) pre-cooled to 0 °C under mechanical stirring. Under vigorous stirring, TCCA (12.8 g, 55 mmol, 1.65 eq.) was added in 4 batches while the reaction temperature was controlled not to exceed 10 °C. The reaction was carried out at 10 °C for a period of 2 hours. After the reaction mixture was stirred continuously at 10 °C for 24 h, the reaction progress was monitored by GC-MS. Subsequently, the reaction mixture was poured into crushed ice (~200 g) and the precipitate was collected by filtration. The pH of the filtrate was adjusted to 2 with concentrated ammonia solution, cooled sufficiently and filtered again. The filtrate was extracted with toluene (6 x 75 mL) to remove the by-product 5,8-dichloroisoquinoline (16). The aqueous phase was further alkalized with concentrated ammonia to pH 6, at which point the precipitate precipitated was filtered, washed with water and dried at room temperature. The final product was purified by recrystallization from methylcyclohexane in 15% yield. 5-Chloroisoquinoline was obtained as 7.60 g (45% yield), melting point 70-72 °C. IR (ATR): 1580, 1489, 1371, 1267, 1204, 1140, 1065, 984, 822, 750, 687, 628, 536 cm?1. 1H NMR (400 MHz, CDCl3): δ= 9.27 (s, 1H), 8.64 (1H). 1H), 8.64 (d, J = 6.0 Hz, 1H), 8.02 (d, J = 6.0 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 7.5 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H).13C NMR (100 MHz, CDCl3): δ= 152.4, 143.9, 133.9, 133.5, 133.5 cm?1. 1H NMR (400 MHz, CDCl3): δ= 152.4, 143.9, 143.9, 133.5 cm? 143.9, 133.7, 131.0, 130.3, 129.4, 127.3, 126.7, 116.9.

References

[1] Inhibitors of SARM1. World Intellectual Property Organization, WO2019236879 A1 2019-12-12.