tert-butylthiourea

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

Procedure: A reaction vessel was charged with 50 ml methanol and 4 g (30 mmol) of tert-butyl thiourea. With this mixture stirred and cooled in an ice bath, there was added over a 5-minute period 7.41 g of (30 mmol) methyl 3-chloro-3-(o-chlorophenyl)pyruvate. The reaction mixture was refluxed for 16 hours. The mixture was cooled to ambient temperature and concentrated under reduced pressure to yield 9.18 g of a yellow solid which became a hard, glass-like material. This material was recrystallized from an acetone-water solution to yield 7.0 g of a yellow solid product (m.p.=159°-161° C.) identified in Table I. cooled in an ice bath The reaction mixture was refluxed for 16 hours concentrated under reduced pressure

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

Procedure: A reaction vessel was charged with 50 ml methanol and 4 g (30 mmol) of tert-butyl thiourea. With this mixture stirred and cooled in an ice bath, there was added over a 5-minute period 7.41 g of (30 mmol) methyl 3-chloro-3-(o-chlorophenyl)pyruvate. The reaction mixture was refluxed for 16 hours. The mixture was cooled to ambient temperature and concentrated under reduced pressure to yield 9.18 g of a yellow solid which became a hard, glass-like material. This material was recrystallized from an acetone-water solution to yield 7.0 g of a yellow solid product (m.p.=159°-161° C.) identified in Table I. cooled in an ice bath The reaction mixture was refluxed for 16 hours concentrated under reduced pressure

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

Procedure: To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (Example 26, Step 2) (0.406 g, 1.09 mmol) in ethanol (11 mL) in a 25 mL round bottom flask was added N-(t-butyl)thiourea (0.144 g, 1.09 mmol) and the solution heated to reflux (14 hours). The reaction was cooled to room temperature. The resulting suspension was concentrated in vacuo, suspended in methylene chloride (100 mL) and washed with NaHCO3 saturated solution (3×10 mL), sodium carbonate solution (10%, 3×20 mL), dried over sodium sulfate, filtered and concentrated. The crude product was recrystallized from methylene chloride and isooctane yielding 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-tert-butylaminothiazole (0.226 g, 51%) as a yellow crystalline plates: mp 250°-253° C.; 1HNMR (DMSO d6) 400 mHz 7.78 (d, J=8.32 Hz, 2 H), 7.70 (s, 1 H), 7.46-7.35 (m, 4 H), 7.15 (t, J=9.05 Hz, 2 H), 3.19 (s, 3 H), 1.40 (s, 9 H); MS m/z 405 (M+H). HRMS Δ=4.78 mmu. the solution heated to reflux (14 hours) The resulting suspension was concentrated in vacuo washed with NaHCO3 saturated solution (3×10 mL), sodium carbonate solution (10%, 3×20 mL) dried over sodium sulfate filtered concentrated The crude product was recrystallized from methylene chloride and isooctane

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

Procedure: The bromomethylketone of example 11 (39.6 mg, 0.078 mmol, 1 equiv.) was dissolved in DMSO (1 mL) and N-tertbutylthiourea (12.4 mg, 0.094 mmol, 1.2 equiv.) was added. The mixture was stirred for 2 h at room temperature. 10 N NaOH (24 μL) was added and after stirring for 4 h at room temperature, another portion of 10 N NaOH (24 μL) was added and the mixture stirred 24 h at room temperature to complete the hydrolysis. The reaction mixture was then neutralized by addition of TFA and the title product of example 12 isolated directly from the reaction mixture by preparative HPLC as a white amorphous TFA salt (21 mg). after stirring for 4 h at room temperature the mixture stirred 24 h at room temperature the hydrolysis

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

Procedure: The bromomethylketone of example 11 (39.6 mg, 0.078 mmol, 1 equiv.) was dissolved in DMSO (1 mL) and N-tertbutylthiourea (12.4 mg, 0.094 mmol, 1.2 equiv.) was added. The mixture was stirred for 2 h at room temperature. 10 N NaOH (24 μL) was added and after stirring for 4 h at room temperature, another portion of 10 N NaOH (24 μL) was added and the mixture stirred 24 h at room temperature to complete the hydrolysis. The reaction mixture was then neutralized by addition of TFA and the title product of example 12 isolated directly from the reaction mixture by preparative HPLC as a white amorphous TFA salt (21 mg). after stirring for 4 h at room temperature the mixture stirred 24 h at room temperature the hydrolysis

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

Procedure: A reaction vessel was charged with 50 ml methanol and 4 g (30 mmol) of tert-butyl thiourea. With this mixture stirred and cooled in an ice bath, there was added over a 5-minute period 7.41 g of (30 mmol) methyl 3-chloro-3-(o-chlorophenyl)pyruvate. The reaction mixture was refluxed for 16 hours. The mixture was cooled to ambient temperature and concentrated under reduced pressure to yield 9.18 g of a yellow solid which became a hard, glass-like material. This material was recrystallized from an acetone-water solution to yield 7.0 g of a yellow solid product (m.p.=159°-161° C.) identified in Table I. cooled in an ice bath The reaction mixture was refluxed for 16 hours concentrated under reduced pressure