Ethanone, 1-imidazo[1,2-a]pyridin-3-yl- (9CI) Chemical Properties

Melting point:

98-99 °C

Density 

1.21±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

3.92±0.50(Predicted)

Appearance

Light yellow to yellow Solid

Safety Information

HS Code 

2933399990

Ethanone, 1-imidazo[1,2-a]pyridin-3-yl- (9CI) Usage And Synthesis

Synthesis

At 0 °C and under inert atmosphere, imidazo[1,2-a]pyridine (8.0 g, 67.7 mmol) was dissolved in carbon disulfide (80 mL) and anhydrous AlCl3 (22.4 g, 169.4 mmol) powder was added slowly. After stirring at room temperature for 30 min, the reaction mixture was gently refluxed and acetic anhydride (6.8 mL, 67.7 mmol) was added dropwise over 30 min. The reaction was continued at reflux temperature for 5 hours. Carbon disulfide was removed by distillation under reduced pressure and the residue was quenched with ice water (200 mL). The aqueous layer was extracted with dichloromethane (2 x 200 mL) and the organic phase was washed sequentially with saturated NaHCO3 solution (2 x 100 mL), water (100 mL) and brine (100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give Int-1 (2.3 g, 22%) as a brown solid.1H NMR (200 MHz, CDCl3): δ 9.67 (d, J = 7Hz, 1H), 8.36 (bs, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.54-7.46 (m, 1H), 7.13-7.06 (m, 1H), 2.61 (s, 3H). Mass spectrum (m/z): 148 [M++1]. Int-1 (5 g, 31.2 mmol) was dissolved in DMFDMA (25 mL) and stirred at reflux under N2 protection for 36 h. After the reaction was monitored for completion by TLC, it was cooled to room temperature, diluted with ether (100 mL) and stirred for 15 min. The solid was collected by filtration, washed with ether (2 x 10 mL) and dried under vacuum to give Int-2 (4.7 g, 70%) as a brown solid.1H NMR (200 MHz, CDCl3): δ 9.82 (d, J = 6.8 Hz, 1H), 8.22 (s, 1H), 7.81 (d, J = 12.2 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 6.97 (t, J = 6.2 Hz, 1H), 5.71 (d, J = 12.2 Hz, 1H), 3.06 (bs, 6H). Mass spectrum (m/z): 216.0 [M++1]. At room temperature and under inert atmosphere, Int-2 (1.3 g, 6.0 mmol) was dissolved in DMF (10 mL), Int-2B (3.5 g, 18.1 mmol) and K2CO3 (2.5 g, 18.1 mmol) were added, and the mixture was heated at 100 °C for 16 hours. After cooling to room temperature, it was poured into ice water (70 mL) and stirred for 15 minutes. The solid was collected by filtration, washed with water (10 mL) and dried under vacuum to give a light brown solid Int-3 (1.1 g, 55%).1H NMR (200 MHz, DMSO-d6): δ 10.11-10.05 (m, 2H), 8.64 (s, 1H), 8.52 (d, J = 5.5Hz, 1H), 7.85-7.63 (m, 5H) , 7.46 (t, J = 7.0 Hz, 1H), 7.32 (d, J = 5.3 Hz, 1H), 7.07 (d, J = 6.2 Hz, 1H), 3.75 (s, 3H). Mass spectrum (m/z): 345.9 [M++1]. Int-3 (0.7 g, 2 mmol) was dissolved in methanol (35 mL) and dichloromethane (14 mL) at 0°C and 50 wt% aqueous hydroxylamine (14 mL) was added. After stirring for 10 min, NaOH solution (0.56 g, dissolved in 3.5 mL of water) was added at 0°C. The reaction mixture was brought to room temperature and stirred for 5 hours. The volatiles were evaporated under reduced pressure and the residue was neutralized with 2N HCl to pH ≈ 7 at 0 °C with stirring for 10 min. The solid was collected by filtration, washed with water (2 x 5 mL) and dried under vacuum. The crude product was purified by preparative HPLC (acetonitrile:water:0.1% trifluoroacetic acid) to afford an off-white solid compound 5 (0.22 g, 31%) in the form of TFA salt.1H NMR (200 MHz, DMSO-d6): δ 11.05 (bs, 1H), 10.2 (d, J = 6.6Hz, 1H), 10.07 (s, 1H), 8.92 (bs, 1H), 8.59 (d, J = 5.6 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.86-7.72 (m, 5H), 7.52 (d, J = 5.2 Hz, 1H), 7.39 (t, J = 6.6 Hz, 1H).13C NMR (120 MHz, DMSO-d6): δ 164.4, 159.0, 158.5, 158.2, 158.0, 156.0, 142.7, 132.1, 131.0, 130.2, 127.6, 125.7, 121.7, 118.4, 115.9, 114.9, 108.2. mass spectrum (m/z): 347.2 [M++1].

References

[1] Patent: US2010/29638, 2010, A1. Location in patent: Page/Page column 65
[2] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 9, p. 2245 - 2248
[3] Patent: EP1214318, 2003, B1. Location in patent: Page/Page column 33
[4] Patent: EP1790650, 2007, A1. Location in patent: Page/Page column 44
[5] Patent: CN103130792, 2016, B. Location in patent: Paragraph 0223-0225

Ethanone, 1-imidazo[1,2-a]pyridin-3-yl- (9CI)(29096-64-8)Related Product Information

• 3,5-DIMETHANOLPYRIDINE
• (1H-IMIDAZOL-2-YL)-METHANOL
• 1H-Imidazol-2-carboxamide
• 4,5-Imidazoledicarboxylic acid
• Imidazole-2-carboxaldehyde