7-Nitroindole

Chemical Properties

yellow crystalline powder

Uses

7-Nitroindole is a reagent used in chemical synthesis. It has been used in the synthesis of protein kinase and inosine monophosphate inhibitors, beta3 agonists and CCK-1 receptor modulators. 7-Nitroindole has also been used as a photochemical precursor of the 2'-deoxyribonolactone analog.

Uses

7-Nitroindole is a useful reactant for the preparation of various compounds and inhibitors.

Uses

Reactant for preparation of:

• Protein kinase inhibitors
• Potential fructose 1,6-bisphosphatase inhibitors
• Factor Xa inhibitors
• Antagonist of the mineralocorticoid receptor
• Antitumor sulfonamides
• Inosine monophosphate dehydrogenase (IMPDH) inhibitors
• Subtype-selective cyclooxygenase (COX) inhibitors
• Thrombin protease-activated receptor (PAR-1) ligands

Application

Reactant for preparation of:
Protein kinase inhibitors
Potential fructose 1,6-bisphosphatase inhibitors
Factor Xa inhibitors
Antagonist of the mineralocorticoid receptor
Antitumor sulfonamides
Inosine monophosphate dehydrogenase (IMPDH) inhibitors
Subtype-selective cyclooxygenase (COX) inhibitors
Thrombin protease-activated receptor (PAR-1) ligands

Synthesis Reference(s)

Canadian Journal of Chemistry, 42, p. 1235, 1964 DOI: 10.1139/v64-189

Synthesis

6960-45-8

6960-42-5

Example 4: Preparation of Compound 4 (7-nitro-1H-indole); Compound 3 (7-nitroindole-2-carboxylic acid, 1.63 g, 7.91 mmol) was dissolved in quinoline (13 mL) followed by addition of copper oxide (CuO, 0.19 g). The reaction mixture was stirred and heated to 194 °C. During heating, gas was observed to escape. After 2 hours of reaction, gas production stopped and the completion of the reaction was confirmed by thin layer chromatography (TLC). The reaction solution was slowly poured into a dilute hydrochloric acid solution prepared from concentrated hydrochloric acid (21.3 mL) and cold water (42.6 mL) and stirred to produce a black precipitate. The reaction mixture was filtered to separate the black precipitate and the filtrate was extracted with ether. The organic phases were combined and washed sequentially with saturated sodium bicarbonate (NaHCO3) solution and deionized water. The organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give a yellow solid. The solid was recrystallized in ethanol (EtOH) to give an acicular light yellow solid, compound 4 (7-nitro-1H-indole, 0.87 g, 69% yield). Melting point 96-97 °C (literature value 95-96 °C); 1H NMR (200 MHz, CDCl3) δ 6.63 (dd, J = 2.2, 1.0 Hz, 1H, ArH), 7.08-7.18 (m, 1H, ArH), 7.32 (t, J = 3.0 Hz, 1H, ArH), 7.90 (d, J = 7.8 Hz, 1H, ArH), 8.08 (d, J = 8.1 Hz, 1H, ArH), 9.88 (s, 1H, NH); 13C NMR (50 MHz, acetone-d6) δ 103.7, 118.9, 119.2, 128.4, 129.1, 129.3, 132.9, 133.5; mass spectrometry (EI) m/z 162 (M+, 100%), 116 (M-46 ), 116 (M-46, 87%), 104 (M-58, 41%), 89 (M-73, 53%).

References

[1] Patent: EP2366687, 2011, A2. Location in patent: Page/Page column 8; 10-11
[2] Journal of the American Chemical Society, 1958, vol. 80, p. 4621
[3] Journal of Organic Chemistry, 1957, vol. 22, p. 84
[4] Journal and Proceedings of the Royal Society of New South Wales, 1938, vol. 72, p. 209,216