1-(3-fluorophenyl)-N-methylmethanamine

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

Procedure: 5-Methylthiazol-2-amine (571 mg, 5.00 mmol) was dissolved into dichloromethane (30 mL) and cooled to near −45° C. Diphosgene (360 μL, 3.0 mmol) was added rapidly over a second or two, and the mixture was stirred for 5 minutes before diisopropylethylamine (1.74 mL, 10 mmol) was added. The solution was stirred for another 30 minutes, 3-fluorobenzyl-methylamine (1.03 mL, 7.5 mmol) was added, and after another couple of minutes, the cold bath was removed. When the reaction solution had warmed to near room temperature, it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL). The aqueous phase was separated and back-extracted with dichloromethane, and the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL). The aqueous phase was separated and back-extracted with dichloromethane. The combined organic phases were dried (sodium sulfate), concentrated, and chromatographed on acidic alumina (ethyl acetate/hexanes) to give the title compound. cooled to near −45° C was added after another couple of minutes, the cold bath was removed it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL) The aqueous phase was separated back-extracted with dichloromethane the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL) The aqueous phase was separated back-extracted with dichloromethane The combined organic phases were dried (sodium sulfate) concentrated chromatographed on acidic alumina (ethyl acetate/hexanes)

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

Procedure: To a solution of 1-({[(2Z)-3-(4-Chlorophenyl)-1,3-thiazolidin-2-ylidene]amino}carbonyl)-3-methyl-1H-imidazol-3-ium iodide (94 mg, 0.209 mmol, Example 25B) in dry acetonitrile (3 mL) were added diisopropylethylamine (0.040 mL, 0.230 mmol) and 1-(3-fluorophenyl)-N-methylmethanamine (0.032 mL, 0.230 mmol). The mixture was heated for 2 hours, and then cooled and concentrated under reduced pressure. The residue was purified by chromatography over silica using dichloromethane:methanol 95:5 as eluent to provide the title compound. The mixture was heated for 2 hours cooled concentrated under reduced pressure The residue was purified by chromatography over silica

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

Procedure: 5-Methylthiazol-2-amine (571 mg, 5.00 mmol) was dissolved into dichloromethane (30 mL) and cooled to near −45° C. Diphosgene (360 μL, 3.0 mmol) was added rapidly over a second or two, and the mixture was stirred for 5 minutes before diisopropylethylamine (1.74 mL, 10 mmol) was added. The solution was stirred for another 30 minutes, 3-fluorobenzyl-methylamine (1.03 mL, 7.5 mmol) was added, and after another couple of minutes, the cold bath was removed. When the reaction solution had warmed to near room temperature, it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL). The aqueous phase was separated and back-extracted with dichloromethane, and the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL). The aqueous phase was separated and back-extracted with dichloromethane. The combined organic phases were dried (sodium sulfate), concentrated, and chromatographed on acidic alumina (ethyl acetate/hexanes) to give the title compound. cooled to near −45° C was added after another couple of minutes, the cold bath was removed it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL) The aqueous phase was separated back-extracted with dichloromethane the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL) The aqueous phase was separated back-extracted with dichloromethane The combined organic phases were dried (sodium sulfate) concentrated chromatographed on acidic alumina (ethyl acetate/hexanes)

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

Procedure: 5-Methylthiazol-2-amine (571 mg, 5.00 mmol) was dissolved into dichloromethane (30 mL) and cooled to near −45° C. Diphosgene (360 μL, 3.0 mmol) was added rapidly over a second or two, and the mixture was stirred for 5 minutes before diisopropylethylamine (1.74 mL, 10 mmol) was added. The solution was stirred for another 30 minutes, 3-fluorobenzyl-methylamine (1.03 mL, 7.5 mmol) was added, and after another couple of minutes, the cold bath was removed. When the reaction solution had warmed to near room temperature, it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL). The aqueous phase was separated and back-extracted with dichloromethane, and the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL). The aqueous phase was separated and back-extracted with dichloromethane. The combined organic phases were dried (sodium sulfate), concentrated, and chromatographed on acidic alumina (ethyl acetate/hexanes) to give the title compound. cooled to near −45° C was added after another couple of minutes, the cold bath was removed it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL) The aqueous phase was separated back-extracted with dichloromethane the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL) The aqueous phase was separated back-extracted with dichloromethane The combined organic phases were dried (sodium sulfate) concentrated chromatographed on acidic alumina (ethyl acetate/hexanes)

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

Procedure: To a solution of 1-({[(2Z)-3-(4-Chlorophenyl)-1,3-thiazolidin-2-ylidene]amino}carbonyl)-3-methyl-1H-imidazol-3-ium iodide (94 mg, 0.209 mmol, Example 25B) in dry acetonitrile (3 mL) were added diisopropylethylamine (0.040 mL, 0.230 mmol) and 1-(3-fluorophenyl)-N-methylmethanamine (0.032 mL, 0.230 mmol). The mixture was heated for 2 hours, and then cooled and concentrated under reduced pressure. The residue was purified by chromatography over silica using dichloromethane:methanol 95:5 as eluent to provide the title compound. The mixture was heated for 2 hours cooled concentrated under reduced pressure The residue was purified by chromatography over silica

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

Procedure: The title compound was prepared in 9% yield from methyl 2-(1-{2-[(methylsulfonyl)oxy]ethyl}-1H-imidazol-4-yl)pyridine-4-carboxylate (PREPARATION 6) and 3-fluoro-N-methylbenzylamine according to the procedure for the preparation of Example 58. 1HNMR (400 MHz, DMSO): δ 2.20 (3H, s), 2.71 (2H, t, J=6.2 Hz), 4.02 (1H, t, J=5.8 Hz), 4.16 (2H, t, J=6.2 Hz), 4.39 (1H, t, J=5.9 Hz), 6.93 (1H, d, J=9.8 Hz), 7.00 (2H, d, J=7.8 Hz), 7.25 (1H, m), 7.57 (1H, m), 7.74 (1H, s), 7.79 (1H, d, J=4.2 Hz), 8.30 (1H, s), 8.59 (1H, m). [M+H] Calc'd for C19H19FN4O2, 355. Found, 355.

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

Procedure: The title compound was prepared in 9% yield from methyl 2-(1-{2-[(methylsulfonyl)oxy]ethyl}-1H-imidazol-4-yl)pyridine-4-carboxylate (PREPARATION 6) and 3-fluoro-N-methylbenzylamine according to the procedure for the preparation of Example 58. 1HNMR (400 MHz, DMSO): δ 2.20 (3H, s), 2.71 (2H, t, J=6.2 Hz), 4.02 (1H, t, J=5.8 Hz), 4.16 (2H, t, J=6.2 Hz), 4.39 (1H, t, J=5.9 Hz), 6.93 (1H, d, J=9.8 Hz), 7.00 (2H, d, J=7.8 Hz), 7.25 (1H, m), 7.57 (1H, m), 7.74 (1H, s), 7.79 (1H, d, J=4.2 Hz), 8.30 (1H, s), 8.59 (1H, m). [M+H] Calc'd for C19H19FN4O2, 355. Found, 355.

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

Procedure: 5-Methylthiazol-2-amine (571 mg, 5.00 mmol) was dissolved into dichloromethane (30 mL) and cooled to near −45° C. Diphosgene (360 μL, 3.0 mmol) was added rapidly over a second or two, and the mixture was stirred for 5 minutes before diisopropylethylamine (1.74 mL, 10 mmol) was added. The solution was stirred for another 30 minutes, 3-fluorobenzyl-methylamine (1.03 mL, 7.5 mmol) was added, and after another couple of minutes, the cold bath was removed. When the reaction solution had warmed to near room temperature, it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL). The aqueous phase was separated and back-extracted with dichloromethane, and the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL). The aqueous phase was separated and back-extracted with dichloromethane. The combined organic phases were dried (sodium sulfate), concentrated, and chromatographed on acidic alumina (ethyl acetate/hexanes) to give the title compound. cooled to near −45° C was added after another couple of minutes, the cold bath was removed it was quenched with 1 M aqueous potassium phosphate monobasic (15 mL) The aqueous phase was separated back-extracted with dichloromethane the combined organic phases were washed with more 1 M aqueous KH2PO4 (5 mL) The aqueous phase was separated back-extracted with dichloromethane The combined organic phases were dried (sodium sulfate) concentrated chromatographed on acidic alumina (ethyl acetate/hexanes)

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

Procedure: To a solution of 1-({[(2Z)-3-(4-Chlorophenyl)-1,3-thiazolidin-2-ylidene]amino}carbonyl)-3-methyl-1H-imidazol-3-ium iodide (94 mg, 0.209 mmol, Example 25B) in dry acetonitrile (3 mL) were added diisopropylethylamine (0.040 mL, 0.230 mmol) and 1-(3-fluorophenyl)-N-methylmethanamine (0.032 mL, 0.230 mmol). The mixture was heated for 2 hours, and then cooled and concentrated under reduced pressure. The residue was purified by chromatography over silica using dichloromethane:methanol 95:5 as eluent to provide the title compound. The mixture was heated for 2 hours cooled concentrated under reduced pressure The residue was purified by chromatography over silica