Ciprofloxacin Related CoMpound synthesis

Yield:-

Reaction Conditions:

in N,N-dimethyl acetamide;water at 0 - 115; for 11.5 h;

Steps:

12; 13 Intermediate 12 and Intermediate 13; 6-[(2-Amino-ethyl)amino]-7-chloro-1-cyclopropyl-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid hydrochloride (12) and 7-[(2-amino-ethyl)amino]-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-quinoline-3-carboxylic acid hydrochloride (13)

7-CHLORO-1-CYCLOPROPYL-1, 4-DIHYDRO-6-FLUORO-4-OXO-QUINOLINE-3-CARBOXYLIC acid (56.3 g) and ethylenediamine (36 G) were dissolved in N, N-DIMETHYLACETAMIDE (650 mL) at 100oC and stirred for 8.5 h at 115oC. Water (700 mL) was added to the reaction mixture cooled at room temperature. The reaction mixture was stirred at room temperature for 2 h, cooled at 0-5oC and stirred for 1 h. The precipitate obtained was filtered, washed with cold water, cold ETOH, and dried at 110oC under reduced pressure for 1 h. The crude product was treated with HCI (6% aqueous solution) heating for 1 h in the presence of charcoal. After filtration, the solution was cooled to 35-40oC and a first precipitation occurred. The precipitate was filtered, washed with water and dried at 110oC FOR 1 h. Intermediate 12 (6.4 g) was obtained as a hydrochloride salt. The mother liquors, after first precipitation, were cooled at room temperature and stirred overnight. The precipitate was filtered, washed with water and dried at 110oC for 1 h to give a mixture containing Intermediates 12 AND 13 (14. 18 G). INTERMEDIATE 12 : 1H-NMR (300 MHz, CF3COOD) d: 8.94 (s, 1H), 8.40 (s, 1 H), 7.40 (s, 1 H), 3.85 (m, 1H), 3.76 (m, 2H), 5.45 (m, 2H), 1.42 (m, 2H), 1.77 (m, 2H).

References:

WO2004/101590,2004,A1 Location in patent:Page 32-33