RN-18

RN-18 Property

Boiling point:

493.6±40.0 °C(Predicted)

Density 

1.36±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMF: 30 mg/ml; DMSO: 30 mg/ml; DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml; Ethanol: slightly soluble

form 

A crystalline solid

pka

12.33±0.70(Predicted)

color 

Light yellow to yellow

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.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

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

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

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

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

RN-18 Chemical Properties,Usage,Production

Uses

RN-18 is a selective inhibitor of?virion infectivity factor (Vif)?APOBEC interactions and HIV-1 replication.

Synthesis

Method A: Synthesis of N-(2-methoxyphenyl)-2-((4-nitrophenyl)thio)benzamide (1) The synthesis of target compound 1 was carried out according to the method described in Scheme 9.The key step of the reaction was the reaction of 2-iodo-N-(2-methoxyphenyl)benzamide 3 with 4-nitrophenylthiophenol 4 via a copper-catalyzed coupling reaction under microwave radiation. First, intermediate compound 3 was prepared in high yield by the reaction of 2-methoxyaniline 5 with 2-iodobenzoyl chloride 2. Scheme 9: (a) The reaction was carried out overnight at 0°C to room temperature in 98% yield using triethylamine as base and dichloromethane as solvent; (b) The reaction was carried out in the presence of potassium carbonate with copper (I) iodide as catalyst and ethylene glycol and 2-propanol as solvents with microwave radiation (150 W, 80 °C) for 30 min (twice) in 63% yield. Synthesis of 2-(4-nitrophenylthio)-N-(2-methoxyphenyl)benzamide (1): 2-Iodo-N-(2-methoxyphenyl)benzamide 3 (0.355 g, 1.0 mmol), copper(I) iodide (20 mg, 0.1 mmol), potassium carbonate (0.276 g, 2.0 mmol), and 4-nitrobenzothiophenol (0.155 g, 1 mmol) were added to a 10 mL reaction tube fitted with a PTFE liner. The reaction tube was evacuated and backfilled with dry nitrogen (cycled three times). Ethylene glycol (0.1 mL, 2.0 mmol) and 2-propanol (1 mL) were added via syringe at room temperature. The reaction tube was placed in a microwave reactor (CEM Explorer) and heated at 80°C and 150 W power for 30 min (twice). After the reaction was completed, it was cooled to room temperature. Ethyl acetate (~10 mL) was added, filtered and the reaction mixture was concentrated. The crude product was purified by rapid column chromatography on silica gel, using a hexane solution of 20% ethyl acetate as eluent. The final product was obtained as 2-(4-nitrophenylthio)-N-(2-methoxyphenyl)benzamide 1 as a light yellow crystalline solid (0.24 g, 63%). 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.0 Hz, 1H), 8.39 (s, 1H, overlapping signals), 8.05 (ddd, J = 9.2, 2.4, 1.6 Hz, 2H), 7.77 (dd, J = 6.4, 2.4 Hz, 1H), 7.56-7.49 (m, 3H), 7.29- 7.25 (m, 2H), 7.06 (ddd, J = 9.2, 7.6, 1.6 Hz, 1H), 6.95 (dt, J = 8.8, 0.8, 1.2 Hz, 1H), 6.85 (dd, J = 8.0, 0.8 Hz, 1H), 3.78 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 165.44, 148.22, 146.87, 146.15, 140.63, 135.76, 131.66, 130.09, 129.87, 129.49, 128.79 (2C), 127.54, 124.54, 124.35 (2C), 121.37, 120.05, 110.19, 55.88. MS (ESI): m/z 402.99 (M + Na)+.

References

[1] Patent: US2007/99919, 2007, A1. Location in patent: Page/Page column 26; 27
[2] ChemMedChem, 2012, vol. 7, # 7, p. 1217 - 1229