7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic Acid Ethyl Ester

Chemical Properties

7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic Acid Ethyl Ester is Light Tan Solid

Uses

7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic Acid Ethyl Ester is a fluoroquinolone derivative used in the preparation of antibacterial agents.

Synthesis

The general procedure for the synthesis of ethyl 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-diazanaphthalene-3-carboxylate from ethyl 3-cyclopropylamino-2-(2,6-dichloro-5-fluoropyridine-3-carbonyl)acrylate (CAS: 96568-06-8) is as follows: at 75-80 °C, 7.0 g of 3-cyclopropylamino-2-( 2,6-dichloro-5-fluoropyridine-3-carbonyl)ethyl acrylate was dissolved in 35 mL of acetonitrile. Subsequently, 8.56 g (2.0 eq.) of K3PO4 was added to the reaction mixture in batches and stirred continuously at the same temperature for 1.5 hours. After completion of the reaction, the mixture was filtered under reduced pressure and the filter cake was washed with 77 mL of dichloromethane. The filtrate was concentrated under reduced pressure and the resulting residue was dissolved in 77 mL of dichloromethane and washed with deionized water. The organic layer was concentrated under reduced pressure to give 6.17 g of the target product ethyl 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-diazanaphthalene-3-carboxylate in 98.5% yield. The structure of the product was confirmed by 1H NMR (CDCl3, ppm): 1.20 (4H, m, CH2CH2), 1.41 (3H, t, J=8 Hz, CH2CH3), 3.66 (1H, m, NCH), 4.41 (2H, q, J=8 Hz, CH2CH3), 8.44 (1H, d, J=4 Hz, C5-H). 8.66 (1H, s, C2-H).

References

[1] Patent: WO2004/56781, 2004, A1. Location in patent: Page 5-6
[2] Tetrahedron Letters, 1988, vol. 29, # 16, p. 1931 - 1934
[3] Patent: WO2004/56781, 2004, A1. Location in patent: Page 15
[4] Journal of Medicinal Chemistry, 1989, vol. 32, # 3, p. 537 - 542
[5] Journal of Medicinal Chemistry, 1992, vol. 35, # 3, p. 518 - 525