5-Methyl-2-[(2-nitrophenyl)amino]thiophene-3-carbonitrile Chemical Properties

Melting point:

109.0 to 115.0 °C

Boiling point:

425.4±45.0 °C(Predicted)

Density 

1.39±0.1 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

Chloroform (Slightly), DMSO (Slightly)

pka

-3.24±0.50(Predicted)

form 

solid

color 

Light yellow to Amber to Dark green

BRN 

7485862

InChI

InChI=1S/C12H9N3O2S/c1-8-6-9(7-13)12(18-8)14-10-4-2-3-5-11(10)15(16)17/h2-6,14H,1H3

InChIKey

NPXUFPFFHANGDL-UHFFFAOYSA-N

SMILES

C1(NC2=CC=CC=C2[N+]([O-])=O)SC(C)=CC=1C#N

CAS DataBase Reference

138564-59-7(CAS DataBase Reference)

Safety Information

Hazard Codes 

N

Risk Statements 

22-50/53

Safety Statements 

22-60-61

RIDADR 

UN 3077 9 / PGIII

HazardClass 

9

PackingGroup 

III

HS Code 

2934990002

5-Methyl-2-[(2-nitrophenyl)amino]thiophene-3-carbonitrile Usage And Synthesis

Chemical Properties

Red Solid

Uses

5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile is an impurity of Olanzapine (O253750). Olanzapine impurity A (EP).

Synthesis

A solution of 1-fluoro-2-nitrobenzene (34.5 g, 244 mmol) and 2-amino-3-cyano-5-methylthiophene (33.1 g, 240 mmol) in anhydrous THF (160 mL) was added slowly and dropwise to a vigorously stirred anhydrous tetrahydrofuran (THF, 100 mL) suspension of sodium hydride (NaH, 13.5 g, 60% dispersed in mineral oil, 336 mmol), cooled in an ice bath, and under nitrogen protection. mmol) in a solution of anhydrous THF (160 mL). After dropwise addition, the reaction mixture was stirred at room temperature for 10 hours. Subsequently, additional sodium hydride (NaH, 1.53 g, 95%, 72 mmol) was slowly added to the reaction mixture and stirring was continued for 8 hours at room temperature. Upon completion of the reaction, the mixture was poured into crushed ice and the pH was adjusted to 8 with saturated ammonium chloride (NH4Cl) solution. the precipitate was collected by filtration and dried to give the crude product. The crude product was purified by silica gel column chromatography (eluent: 10% ethyl acetate/hexane) to afford 2-(2-nitroanilino)-3-cyano-5-methylthiophene (47.9 g, 77% yield) as a dark solid. Thin layer chromatography (TLC) Rf value was 0.62 (25% ethyl acetate/hexane). The melting point is 105-107°C. Nuclear magnetic resonance hydrogen spectrum (1H NMR, CDCl3): δ 2.47 (d, J = 1.0 Hz, 3H, CH3), 6.78 (q, J = 1.0 Hz, 1H, Ar-H), 6.95 (ddd, J = 1.0, 7.0, 8.5 Hz, 1H, Ph-H), 7.18 (dd, J = 1.0, 8.5 Hz, 1H, Ph-H) , 7.50 (dd, J = 1.5, 7.0, 8.5 Hz, 1H, Ph-H), 8.24 (dd, J = 1.5, 8.5 Hz, 1H, Ph-H), 9.61 (s, 1H, NH). Mass spectrum (MS, ESI): m/z 258 ([M-H]? , 100%).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 7, p. 1953 - 1956
[2] Patent: US2010/266711, 2010, A1. Location in patent: Page/Page column 14
[3] Patent: WO2008/50341, 2008, A2. Location in patent: Page/Page column 33
[4] Patent: WO2004/94390, 2004, A1. Location in patent: Page 13-14
[5] Russian Journal of Bioorganic Chemistry, 2005, vol. 31, # 4, p. 378 - 382

5-Methyl-2-[(2-nitrophenyl)amino]thiophene-3-carbonitrile(138564-59-7)Related Product Information

• 4-Amino-2-methyl-10H-thiene[2,3-b][1,5]benzodiazepine hydrochloride
• Olanzapine Impurity(ADP-2b)
• 2-Amino-5-methyl-3-thiophenecarbonitrile
• Olanzapine dimer
• Olanzapine Impurity K
• (E)-1-(4-(2-Methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-yl)ethanone
• 1-(ChloroMethyl)-1-Methyl-4-(2-Methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl)-piperaziniuM Chloride
• 2-(1,2-PhenylenediaMino)-5-Methylthiphene-3-carbonitrile
• Olanzapine ThioacetoxyMethylidene IMpurity Discontinued
• Olanzapine ThiolactaM IMpurity
• HydroxyMethylidene thione
• Olanzapine LactaM IMpurity
• 2-Propylidenepropanedinitrile
• 2-CHLORO-6-METHYL-4-NITROANILINE
• 5-Nitroanthranilonitrile
• IMp. A (EP): 5-Methyl-2-[(2-nitrophenyl)-aMino]thiophene-3-carbonitrile
• Olanzapine Benzoate
• Olanzapine Impurity(ADP-2c)