(2-fluorophenyl)thiourea

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

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

Procedure: To a suspension of (2-fluorophenyl)thiourea (1.7 g, 10.0 mmol) in chloroform (25 ml) was added a solution of bromine (0.51 mL; 10.0 mmol) dropwise at room temperature. The resulting mixture was heated under reflux for 3 hrs. The solvent was evaporated, water was added and the mixture was neutralized with ammonium hydroxide. The resulting white precipitation was collected by filtration and dried to yield 1.2 g (72%) of the title compound which was used in the subsequent step without further purification. The resulting mixture was heated under reflux for 3 hrs The solvent was evaporated water was added The resulting white precipitation was collected by filtration dried

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

Procedure: To a stirred solution of 3.0 g (0.017 mol) of N-(2-fluorophenyl)thiourea in 75 ml of acetone was added an excess of methyl iodide. The reaction was allowed to stir over night. To the solution was then added 20 ml of cyclohexane; a white solid crystallized and was collected by filtration to yield 4.3 g of N-(2-fluorophenyl)-S-methylisothiourea. a white solid crystallized was collected by filtration

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

Procedure: To a stirred solution of 7.0 g (0.045 mol) of 2-fluorophenyl isothiocyanate in 100 ml of ether, was added ammonia gas over a three minute period. A white solid crystallized and was collected by filtration to yield 5.3 g of N-(2- fluorophenyl)thiourea. melting point 147-148° C. A white solid crystallized was collected by filtration

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

Procedure: To a stirred solution of 7.0 g (0.045 mol) of 2-fluorophenyl isothiocyanate in 100 ml of ether, was added ammonia gas over a three minute period. A white solid crystallized and was collected by filtration to yield 5.3 g of N-(2- fluorophenyl)thiourea. melting point 147-148° C. A white solid crystallized was collected by filtration

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

Procedure: To a suspension of (2-fluorophenyl)thiourea (1.7 g, 10.0 mmol) in chloroform (25 ml) was added a solution of bromine (0.51 mL; 10.0 mmol) dropwise at room temperature. The resulting mixture was heated under reflux for 3 hrs. The solvent was evaporated, water was added and the mixture was neutralized with ammonium hydroxide. The resulting white precipitation was collected by filtration and dried to yield 1.2 g (72%) of the title compound which was used in the subsequent step without further purification. The resulting mixture was heated under reflux for 3 hrs The solvent was evaporated water was added The resulting white precipitation was collected by filtration dried

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

Procedure: To a suspension of (2-fluorophenyl)thiourea (1.7 g, 10.0 mmol) in chloroform (25 ml) was added a solution of bromine (0.51 mL; 10.0 mmol) dropwise at room temperature. The resulting mixture was heated under reflux for 3 hrs. The solvent was evaporated, water was added and the mixture was neutralized with ammonium hydroxide. The resulting white precipitation was collected by filtration and dried to yield 1.2 g (72%) of the title compound which was used in the subsequent step without further purification. The resulting mixture was heated under reflux for 3 hrs The solvent was evaporated water was added The resulting white precipitation was collected by filtration dried

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

Procedure: To a suspension of (2-fluorophenyl)thiourea (1.7 g, 10.0 mmol) in chloroform (25 ml) was added a solution of bromine (0.51 mL; 10.0 mmol) dropwise at room temperature. The resulting mixture was heated under reflux for 3 hrs. The solvent was evaporated, water was added and the mixture was neutralized with ammonium hydroxide. The resulting white precipitation was collected by filtration and dried to yield 1.2 g (72%) of the title compound which was used in the subsequent step without further purification. The resulting mixture was heated under reflux for 3 hrs The solvent was evaporated water was added The resulting white precipitation was collected by filtration dried

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

Procedure: To a suspension of (2-fluorophenyl)thiourea (1.7 g, 10.0 mmol) in chloroform (25 ml) was added a solution of bromine (0.51 mL; 10.0 mmol) dropwise at room temperature. The resulting mixture was heated under reflux for 3 hrs. The solvent was evaporated, water was added and the mixture was neutralized with ammonium hydroxide. The resulting white precipitation was collected by filtration and dried to yield 1.2 g (72%) of the title compound which was used in the subsequent step without further purification. The resulting mixture was heated under reflux for 3 hrs The solvent was evaporated water was added The resulting white precipitation was collected by filtration dried

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

Procedure: To a stirred solution of 3.0 g (0.017 mol) of N-(2-fluorophenyl)thiourea in 75 ml of acetone was added an excess of methyl iodide. The reaction was allowed to stir over night. To the solution was then added 20 ml of cyclohexane; a white solid crystallized and was collected by filtration to yield 4.3 g of N-(2-fluorophenyl)-S-methylisothiourea. a white solid crystallized was collected by filtration

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

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

Procedure: Methyl 4-(2-bromoacetyl)-5-methylthiothiophene-2-carboxylate (60 mg, 0.19 mmol) was allowed to react with 2-fluorophenyl thiourea as described in Example 154, step (a) to give 55.6 mg (70% yield) of methyl 4-{2-[(2-fluorophenyl)amino](1,3-thiazol-4-yl)}-5-methylthiothiophene-2-carboxylate hydrobromide. 1H NMR (DMSO-d6, 300 MHz) δ2.68 (s, 3H), 3.83 (s, 3H), 6.96-7.04 (m, 1H), 7.14-7.29 (m, 3H), 7.35 (s, 1H), 8.06, 8.14 (s, 1H rotomer), 8.53, 8.8.68 (td, 1H rotomer, J=1.5, 8.5 Hz), 10.14, 10.30 (s, 1H rotomer); Mass Spectrum (ESI) m/z calcd. for C16H13FN2O2S3, 380.48 (M+H), found 381.1.