2-bromo-1-phenylpropan-1-one

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:

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

Procedure: Methyl-4-[(5-methyl-4-phenyl(1,3-thiazol-2-yl)amino]-5-methylthiothiophene-2-carboxylate: Using a procedure similar to Example 204, step (a), 51 mg (0.19 mmol) of methyl 4-[(aminothioxomethyl)amino]-5-methylthiothiophene-2-carboxylate was allowed to react with 41.4 mg (0.38 mmol) of 2-bromopropiophenone (Aldrich Chemical Co., Milwaukee, Wis.) in 2 mL of DMF for 4 h. Concentration in vacuo of the reaction mixture afforded 73 mg (100%) of methyl-4-[(5-methyl-4-phenyl(1,3-thiazol-2-yl))amino]-5-methylthiothiophene-2-carboxylate. Mass spectrum (ESI, m/z): Calcd. for C17H16N2O2S3, 377.05 (M+H), found 377.2. Concentration in vacuo of the reaction mixture

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

Procedure: To a mixture of 1-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)guanidine bis-TFA salt (0.200 g, 0.35 mmol) and potassium carbonate (0.20 g, 1.4 mmol) in 1 mL DMSO was added 2-bromo-1-phenylpropan-1-one (0.054 ml, 0.35 mmol). The reaction was allowed to stir at ambient temperature for 30 min, then 70° C. After 16 h, the reaction was quenched by addition of water and was extracted with EtOAc. The organic layer was dried over anhyd. Sodium sulfate, filtered, and concentrated in vacuo. The resulting green/brown oil was purified by silica gel chromatography (40 g, 0-100% 90/10 MC/MeOH in MC) to give an oil. This was lyophilized from MeOH/water to give N-methyl-4-(2-(4-(5-methyl-4-phenyl-1H-imidazol-2-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-amine as an off-white solid. MS m/z=450 [M+H]+. Calc'd for C26H23N7O: 449.5. 70° C After 16 h the reaction was quenched by addition of water was extracted with EtOAc The organic layer was dried over anhyd Sodium sulfate, filtered concentrated in vacuo The resulting green/brown oil was purified by silica gel chromatography (40 g, 0-100% 90/10 MC/MeOH in MC) to give an oil

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

Procedure: To a mixture of 1-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)guanidine bis-TFA salt (0.200 g, 0.35 mmol) and potassium carbonate (0.20 g, 1.4 mmol) in 1 mL DMSO was added 2-bromo-1-phenylpropan-1-one (0.054 ml, 0.35 mmol). The reaction was allowed to stir at ambient temperature for 30 min, then 70° C. After 16 h, the reaction was quenched by addition of water and was extracted with EtOAc. The organic layer was dried over anhyd. Sodium sulfate, filtered, and concentrated in vacuo. The resulting green/brown oil was purified by silica gel chromatography (40 g, 0-100% 90/10 MC/MeOH in MC) to give an oil. This was lyophilized from MeOH/water to give N-methyl-4-(2-(4-(5-methyl-4-phenyl-1H-imidazol-2-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-amine as an off-white solid. MS m/z=450 [M+H]+. Calc'd for C26H23N7O: 449.5. 70° C After 16 h the reaction was quenched by addition of water was extracted with EtOAc The organic layer was dried over anhyd Sodium sulfate, filtered concentrated in vacuo The resulting green/brown oil was purified by silica gel chromatography (40 g, 0-100% 90/10 MC/MeOH in MC) to give an oil

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

Procedure: To a solution of 2-bromo-1-phenylpropan-1-one (25 g) in acetonitrile (250 ml) was added formic acid (7.7 ml), and thereto was added dropwise triethylamine (25 ml) under ice-cooling. Then, the mixture was stirred at room temperature for 5 hours. After the reaction was completed, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate solution was washed with water and aqueous sodium chloride solution, dried over magnesium sulfate, and filtered and concentrated to give the title compound (19 g). The obtained crude product was used in the next reaction without further purification. cooling the mixture was extracted with ethyl acetate The ethyl acetate solution was washed with water and aqueous sodium chloride solution dried over magnesium sulfate filtered concentrated

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

Procedure: To a solution of 2-bromo-1-phenylpropan-1-one (25 g) in acetonitrile (250 ml) was added formic acid (7.7 ml), and thereto was added dropwise triethylamine (25 ml) under ice-cooling. Then, the mixture was stirred at room temperature for 5 hours. After the reaction was completed, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate solution was washed with water and aqueous sodium chloride solution, dried over magnesium sulfate, and filtered and concentrated to give the title compound (19 g). The obtained crude product was used in the next reaction without further purification. cooling the mixture was extracted with ethyl acetate The ethyl acetate solution was washed with water and aqueous sodium chloride solution dried over magnesium sulfate filtered concentrated

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

Procedure: There was added 10.08 parts of sodium bicarbonate and about 60 parts of water to a mixture of 21.3 parts of α-bromopropiophenone, 6.8 parts of sodium formate and about 90 parts of acetonitrile. The resulting mixture was stirred vigorously for 48 hours at 65° C. during which time carbon dioxide evolved. After cooling, the acetonitrile solution was separated from the aqueous layer and evaporated to dryness. The residue was dissolved into chloroform which was extracted once with water, dried over sodium sulfate, and evaporated to produce analytically pure (>98%) α-hydroxypropiophenone. The yield of this isolated product was 77.1%. After cooling the acetonitrile solution was separated from the aqueous layer evaporated to dryness The residue was dissolved into chloroform which was extracted once with water dried over sodium sulfate evaporated

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

Procedure: Methyl-4-[(5-methyl-4-phenyl(1,3-thiazol-2-yl)amino]-5-methylthiothiophene-2-carboxylate: Using a procedure similar to Example 204, step (a), 51 mg (0.19 mmol) of methyl 4-[(aminothioxomethyl)amino]-5-methylthiothiophene-2-carboxylate was allowed to react with 41.4 mg (0.38 mmol) of 2-bromopropiophenone (Aldrich Chemical Co., Milwaukee, Wis.) in 2 mL of DMF for 4 h. Concentration in vacuo of the reaction mixture afforded 73 mg (100%) of methyl-4-[(5-methyl-4-phenyl(1,3-thiazol-2-yl))amino]-5-methylthiothiophene-2-carboxylate. Mass spectrum (ESI, m/z): Calcd. for C17H16N2O2S3, 377.05 (M+H), found 377.2. Concentration in vacuo of the reaction mixture

Conditions: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-1-phenyl-propan-1-one (3.64 g, 17.1 mmol) in 30 mL of ethanol was added thiourea (1.30 g, 1.00 eq.) and the mixture vigorously stirred at 55-60° C. for 4 h. Pouring onto crashed ice/Na2CO3, twofold extraction with ethyl acetate, washing with water and brine, drying over sodium sulfate, and evaporation of the solvents, followed by crystallization from ethyl acetate/hexane, left 2.87 g of the title product as off-white crystals. Pouring ice/Na2CO3, twofold extraction with ethyl acetate washing with water and brine drying over sodium sulfate, and evaporation of the solvents followed by crystallization from ethyl acetate/hexane left 2.87 g of the title product as off-white crystals