1-chloro-2-ethenyl-3-fluorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2-chloro-6-fluorobenzaldehyde (Aldrich), was converted to 2-chloro-6-fluorostyrene according to the method described in Example 377 of WO 93/03022 and then to cis-2-(2-chloro-6-fluorophenyl) cyclopropylisocyanate analogously to the method described in Example 348 of WO 93/03022. This compound was then condensed with 2-amino-5-cyanopyridine of Example 41 in a manner analogous to the method in Example 7 to provide N-(cis-2-(2-chloro-6-fluorophenyl)-cyclopropyl)-N′-(5-cyanopyrid-2-yl)-urea: Mp 189° C. 1H -NMR (250 MHz, DMSO-d6): 1.2 (m, 11H), 1.45-1.55 (m, 1H), 2.2-2.3 (m, 1H), 3.3-3.4 (m, 1H), 7.35-7.6 (m, 41z), 7.9-8.1 (m, 2H), 9.5 (s, 1).

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

Procedure: 2-chloro-6-fluorobenzaldehyde (Aldrich), was converted to 2-chloro-6-fluorostyrene according to the method described in Example 377 of WO 93/03022 and then to cis-2-(2-chloro-6-fluorophenyl) cyclopropylisocyanate analogously to the method described in Example 348 of WO 93/03022. This compound was then condensed with 2-amino-5-cyanopyridine of Example 41 in a manner analogous to the method in Example 7 to provide N-(cis-2-(2-chloro-6-fluorophenyl)-cyclopropyl)-N′-(5-cyanopyrid-2-yl)-urea: Mp 189° C. 1H -NMR (250 MHz, DMSO-d6): 1.2 (m, 11H), 1.45-1.55 (m, 1H), 2.2-2.3 (m, 1H), 3.3-3.4 (m, 1H), 7.35-7.6 (m, 41z), 7.9-8.1 (m, 2H), 9.5 (s, 1).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution (120 mL) of 1-chloro-3-fluoro-2-vinylbenzene (9.45 g) in ethyl acetate were added sodium acetate (4.92 g) and 10% Pd/C (50% water-containing product, 0.95 g), and the mixture was vigorously stirred under a hydrogen atmosphere. The catalyst was filtered off, and the filtrate was concentrated. The residue was partitioned with ethyl acetate-water. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to give the title compound as a colorless oil (yield: 8.4 g). The catalyst was filtered off the filtrate was concentrated The residue was partitioned with ethyl acetate-water The organic layer was washed with saturated brine dried over anhydrous sodium sulfate concentrated

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

Procedure: Under an argon atmosphere, to a suspension (1.1 L) of methyltriphenylphosphonium bromide (90 g) in dry tetrahydrofuran was added a solution (264 mL) of 1 mol/L-potassium tert-butoxide in tetrahydrofuran with stirring under ice-cooling, and the mixture was stirred at the same temperature for 30 min. Then, a solution (165 mL) of 2-chloro-6-fluorobenzaldehyde (34.5 g) in tetrahydrofuran was added to the mixture, and the mixture was stirred for 30 min. The insoluble material was removed with celite, and the filtrate was concentrated under reduced pressure. Ethyl acetate was added to the residue and, after triturating, the crystals were collected by filtration and concentrated. The residue was purified by silica gel column chromatography (developing solvent: hexane) using NH-silica gel (manufactured by Fuji Silysia Chemical Ltd.) to give the title compound as a colorless oil (yield: 20.7 g). cooling the mixture was stirred at the same temperature for 30 min the mixture was stirred for 30 min The insoluble material was removed with celite the filtrate was concentrated under reduced pressure Ethyl acetate was added to the residue after triturating the crystals were collected by filtration concentrated The residue was purified by silica gel column chromatography (developing solvent: hexane)

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

Procedure: 2-chloro-6-fluorobenzaldehyde (Aldrich), was converted to 2-chloro-6-fluorostyrene according to the method described in Example 377 of WO 93/03022 and then to cis-2-(2-chloro-6-fluorophenyl) cyclopropylisocyanate analogously to the method described in Example 348 of WO 93/03022. This compound was then condensed with 2-amino-5-cyanopyridine of Example 41 in a manner analogous to the method in Example 7 to provide N-(cis-2-(2-chloro-6-fluorophenyl)-cyclopropyl)-N'-(5-cyanopyrid-2-yl)-urea: Mp 189° C. 1H-NMR (250 MHz, DMSO-d6): 1.2 (m, 1H), 1.45-1.55 (m, 1H), 2.2-2.3 (m, 1H), 3.3-3.4 (m, 1H), 7.35-7.6 (m, 4H), 7.9-8.1 (m, 2H), 9.5 (s, 1H).

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

Procedure: 2-chloro-6-fluorobenzaldehyde (Aldrich), was converted to 2-chloro-6-fluorostyrene according to the method described in Example 377 of WO 93/03022 and then to cis-2-(2-chloro-6-fluorophenyl) cyclopropylisocyanate analogously to the method described in Example 348 of WO 93/03022. This compound was then condensed with 2-amino-5-cyanopyridine of Example 41 in a manner analogous to the method in Example 7 to provide N-(cis-2-(2-chloro-6-fluorophenyl)-cyclopropyl)-N′-(5-cyanopyrid-2-yl)-urea: Mp 189° C. 1H -NMR (250 MHz, DMSO-d6): 1.2 (m, 11H), 1.45-1.55 (m, 1H), 2.2-2.3 (m, 1H), 3.3-3.4 (m, 1H), 7.35-7.6 (m, 41z), 7.9-8.1 (m, 2H), 9.5 (s, 1).