1-amino-3-(4-chlorophenyl)urea

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from N-p-chlorophenylhydrazine carboxamide and 1-[3-(7-fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl-]ethanone in analogy to the synthesis of example 1. 1H-NMR (400 MHz, DMSO-d6) δ ppm 10.20 (s, 1H), 9.18 (s, 1H), 8.86 (dd, 1H), 8.31 (m, 2H), 8.07 (d, 1H), 7.96 (d, 1H), 7.78 (d, 1H), 7.67 (m, 3H), 7.48 (q, 1H), 7.36 (d, 2H), 4.58 (s, 2H), 2.32 (s, 3H). LCMS (method C): [MH]+=489, tR=4.35 min.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from N-p-chlorophenylhydrazine carboxamide and 1-[3-(7-fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl-]ethanone in analogy to the synthesis of example 1. 1H-NMR (400 MHz, DMSO-d6) δ ppm 10.20 (s, 1H), 9.18 (s, 1H), 8.86 (dd, 1H), 8.31 (m, 2H), 8.07 (d, 1H), 7.96 (d, 1H), 7.78 (d, 1H), 7.67 (m, 3H), 7.48 (q, 1H), 7.36 (d, 2H), 4.58 (s, 2H), 2.32 (s, 3H). LCMS (method C): [MH]+=489, tR=4.35 min.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(p-Chlorophenyl)semicarbazide (1.49 g, 8.03 mmol) is added to a solution of 2-(trifluoromethyl)-4H-3,1-benzoxazin-4-one (1.72 g, 8.00 mmol) in pyridine (27 mL) at 100° C. The reaction mixture is stirred for 15 hours at 100° C., cooled to room temperature and concentrated in vacuo to obtain a solid. The solid is diluted with dichloromethane and the mixture is washed sequentially with 10% hydrochloric acid and water and concentrated in vacuo to obtain a tan solid. The tan solid is washed with dichloromethane and filtered. The filtrate is concentrated in vacuo to obtain a brown foam. The foam is diluted with ether and the mixture is washed sequentially with 10% hydrochloric acid, water and saturated sodium hydrogen carbonate solution, dried over anhydrous MgSO4, decolorized with carbon and concentrated in vacuo to obtain a cream colored foam. Flash chromatography of the cream colored foam using silica gel and a 3:1 dichloromethane/hexanes solution gives the title product as a white solid, 0.36 g, which is identified by 1HNMR spectral analysis. cooled to room temperature concentrated in vacuo to obtain a solid the mixture is washed sequentially with 10% hydrochloric acid and water concentrated in vacuo to obtain a tan solid The tan solid is washed with dichloromethane filtered The filtrate is concentrated in vacuo to obtain a brown foam the mixture is washed sequentially with 10% hydrochloric acid, water and saturated sodium hydrogen carbonate solution dried over anhydrous MgSO4 concentrated in vacuo to obtain a cream colored foam

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrazine (0.83 mL, 26.4 mmol) is added dropwise to a solution of 4-chlorophenyl isocyanate (3.85 g, 25.1 mmol) in 1,2-dichloroethane. The reaction mixture is stirred overnight at room temperature and filtered. The filter cake is washed with ether and dried to give the title product as a white solid, 4.28 g, which is identified by 1HNMR spectral analysis. filtered The filter cake is washed with ether dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrazine (0.83 mL, 26.4 mmol) is added dropwise to a solution of 4-chlorophenyl isocyanate (3.85 g, 25.1 mmol) in 1,2-dichloroethane. The reaction mixture is stirred overnight at room temperature and filtered. The filter cake is washed with ether and dried to give the title product as a white solid, 4.28 g, which is identified by 1HNMR spectral analysis. filtered The filter cake is washed with ether dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from N-p-chlorophenylhydrazine carboxamide and 1-[3-(7-fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl-]ethanone in analogy to the synthesis of example 1. 1H-NMR (400 MHz, DMSO-d6) δ ppm 10.20 (s, 1H), 9.18 (s, 1H), 8.86 (dd, 1H), 8.31 (m, 2H), 8.07 (d, 1H), 7.96 (d, 1H), 7.78 (d, 1H), 7.67 (m, 3H), 7.48 (q, 1H), 7.36 (d, 2H), 4.58 (s, 2H), 2.32 (s, 3H). LCMS (method C): [MH]+=489, tR=4.35 min.