2-Methyl-4-nitroindole Chemical Properties

Melting point:

192-194 °C

Boiling point:

365.6±22.0 °C(Predicted)

Density 

1.355±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

15.34±0.30(Predicted)

Appearance

Yellow to brown Solid

Safety Information

Hazard Codes 

Xi

HazardClass 

IRRITANT

HS Code 

2933998090

2-Methyl-4-nitroindole Usage And Synthesis

Uses

2-Methyl-4-nitroindole is a useful synthetic intermediate in the synthesis of AZD1981, a CRTH2 receptor antagonist used in patients with moderate to severe COPD. 2-Methyl-4-nitroindole is also used as a reagent in the preparation of anti-angiogenic pyrroloazaflavones.

Synthesis Reference(s)

Tetrahedron Letters, 40, p. 5395, 1999 DOI: 10.1016/S0040-4039(99)01014-X

Synthesis

In a 125 mL Erlenmeyer flask, 3-nitroaniline (1.00 g, 7.24 mmol) and acetone (0.74 mL, 0.59 g, 10 mmol) were dissolved in 20 mL of dimethyl sulfoxide (DMSO). Potassium tert-butoxide (1.95 g, 17.4 mmol) was added to the solution and the reaction mixture was stirred at room temperature for 2 h until LC-MS analysis showed that most of the feedstock had been consumed. Upon completion of the reaction, the reaction was quenched by the addition of 85 mL of saturated ammonium chloride solution, followed by extraction with ethyl acetate (3 × 75 mL). The organic phases were combined, washed with 60 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by fast column chromatography on silica gel, the eluent being a hexane solution of 6-50% ethyl acetate, to afford the target compound 2-methyl-4-nitroindole (0.56 g, 44% yield). The structure of the product was confirmed by 1H NMR (DMSO-d6): δ 11.85 (br.s, 1H), 7.99 (dd, J = 8.1, 1.0 Hz, 1H), 7.74 (dt, J = 8.0, 0.8 Hz, 1H), 7.19 (t, J = 8.0 Hz, 1H), 6.80 (t, J = 0.9 Hz, 1H), 2.49 (d , J = 0.8 Hz, 3H).

References

[1] Tetrahedron Letters, 1999, vol. 40, # 29, p. 5395 - 5398
[2] Patent: US2011/105509, 2011, A1. Location in patent: Page/Page column 31; 32
[3] Patent: EP2762476, 2014, A1. Location in patent: Paragraph 0206

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