2-(2,4,6-trimethylphenyl)acetaldehyde

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

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

Procedure: A solution of dimethylsulfoxide (468 mg, 6.00 mmol) and acetonitrile (8 ml) was added to a mixture of mesitylacetoaldehyde (904 mg, 5.57 mmol), bromotrimethylsilane (919 mg, 6.00 mmol) and acetonitrile (8 ml) at 0° C. After stirring at room temperature for 0.5 hour, the mixture was diluted with water (70 ml) and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo. A mixture of the residue, 2-amino-6-(methylamino)pyrimidin-4-ol (1.69 g, 6.00 mmol), potassium carbonate (50 mg) and dimethylsulfoxide (3 ml) was heated at 100° C. for 1 hour. After cooling, the mixture was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (1:1) to give 1.07 g (68%) of the title compound. extracted with ethyl acetate (100 ml×2) washed with brine dried over sodium sulfate concentrated in vacuo was heated at 100° C. for 1 hour After cooling extracted with ethyl acetate (100 ml×2) washed with saturated aqueous sodium hydrogen carbonate and brine dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (1:1)

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

Procedure: A solution of dimethylsulfoxide (468 mg, 6.00 mmol) and acetonitrile (8 ml) was added to a mixture of mesitylacetoaldehyde (904 mg, 5.57 mmol), bromotrimethylsilane (919 mg, 6.00 mmol) and acetonitrile (8 ml) at 0° C. After stirring at room temperature for 0.5 hour, the mixture was diluted with water (70 ml) and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo. A mixture of the residue, 2-amino-6-(methylamino)pyrimidin-4-ol (1.69 g, 6.00 mmol), potassium carbonate (50 mg) and dimethylsulfoxide (3 ml) was heated at 100° C. for 1 hour. After cooling, the mixture was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (1:1) to give 1.07 g (68%) of the title compound. extracted with ethyl acetate (100 ml×2) washed with brine dried over sodium sulfate concentrated in vacuo was heated at 100° C. for 1 hour After cooling extracted with ethyl acetate (100 ml×2) washed with saturated aqueous sodium hydrogen carbonate and brine dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (1:1)

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

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

Procedure: Mesitylacetaldehyde (0.68 g, 4.19 mmol) was dissolved in THF (5.0 mL, dry) and MeMgBr in Et2O (3.0M, 0.75 g, 6.29 mmol)) was added slowly at 0° C. The cooling bath was removed and the reaction mixture was stirred at rt for 4.5 h. The mixture was cooled to 0° C. and excess Grignard reagent was hydrolyzed with HCl (1N). The mixture was diluted with water and extracted with Et2O. The organic layer was dried over Na2SO4, evaporated and the residue was purified by column chromatography on silica gel using MTBE, heptane and DCM as eluant giving the title compound (0.51 g, 61%). 1H NMR (CDCl3, 500 MHz) δ 6.88-6.85 (m, 2H), 4.08-3.99 (m, 1H), 2.87-2.72 (m, 2H), 2.32 (s, 6H), 2.26 (s, 3H), 1.29 (d, 3H). The cooling bath was removed The mixture was cooled to 0° C. The mixture was diluted with water extracted with Et2O The organic layer was dried over Na2SO4 evaporated the residue was purified by column chromatography on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Mesitylethanol (0.99 g, 6.0 mmol) was dissolved in DCM (10.0 mL, dry) and cooled to 0° C. 1,1,1-Tris(acetyloxy)-1λ5,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) in DCM (15 wt %, 2.80 g, 6.60 mmol) was added dropwise over a period of 20 mins. The ice bath was removed and the reaction mixture was stirred at rt for 4 h. NaOH (2N, 5 mL) was added to the mixture and it was diluted with water (5 mL). The layers were separated and the organic layer was washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica gel using heptane and EtOAc as eluant giving the title compound (0.69 g, 71%). 1H NMR (CDCl3, 400 MHz) δ 9.68-9.65 (m, 1H), 6.94-6.90 (m, 2H), 3.75-3.71 (m, 2H), 2.29 (s, 3H), 2.27 (s, 6H). The ice bath was removed NaOH (2N, 5 mL) was added to the mixture and it was diluted with water (5 mL) The layers were separated the organic layer was washed with water dried over Na2SO4 evaporated The residue was purified by column chromatography on silica gel

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

Procedure: Mesitylacetaldehyde (0.68 g, 4.19 mmol) was dissolved in THF (5.0 mL, dry) and MeMgBr in Et2O (3.0M, 0.75 g, 6.29 mmol)) was added slowly at 0° C. The cooling bath was removed and the reaction mixture was stirred at rt for 4.5 h. The mixture was cooled to 0° C. and excess Grignard reagent was hydrolyzed with HCl (1N). The mixture was diluted with water and extracted with Et2O. The organic layer was dried over Na2SO4, evaporated and the residue was purified by column chromatography on silica gel using MTBE, heptane and DCM as eluant giving the title compound (0.51 g, 61%). 1H NMR (CDCl3, 500 MHz) δ 6.88-6.85 (m, 2H), 4.08-3.99 (m, 1H), 2.87-2.72 (m, 2H), 2.32 (s, 6H), 2.26 (s, 3H), 1.29 (d, 3H). The cooling bath was removed The mixture was cooled to 0° C. The mixture was diluted with water extracted with Et2O The organic layer was dried over Na2SO4 evaporated the residue was purified by column chromatography on silica gel

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

Procedure: Mesitylacetaldehyde (0.68 g, 4.19 mmol) was dissolved in THF (5.0 mL, dry) and MeMgBr in Et2O (3.0M, 0.75 g, 6.29 mmol)) was added slowly at 0° C. The cooling bath was removed and the reaction mixture was stirred at rt for 4.5 h. The mixture was cooled to 0° C. and excess Grignard reagent was hydrolyzed with HCl (1N). The mixture was diluted with water and extracted with Et2O. The organic layer was dried over Na2SO4, evaporated and the residue was purified by column chromatography on silica gel using MTBE, heptane and DCM as eluant giving the title compound (0.51 g, 61%). 1H NMR (CDCl3, 500 MHz) δ 6.88-6.85 (m, 2H), 4.08-3.99 (m, 1H), 2.87-2.72 (m, 2H), 2.32 (s, 6H), 2.26 (s, 3H), 1.29 (d, 3H). The cooling bath was removed The mixture was cooled to 0° C. The mixture was diluted with water extracted with Et2O The organic layer was dried over Na2SO4 evaporated the residue was purified by column chromatography on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Mesitylethanol (0.99 g, 6.0 mmol) was dissolved in DCM (10.0 mL, dry) and cooled to 0° C. 1,1,1-Tris(acetyloxy)-1λ5,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) in DCM (15 wt %, 2.80 g, 6.60 mmol) was added dropwise over a period of 20 mins. The ice bath was removed and the reaction mixture was stirred at rt for 4 h. NaOH (2N, 5 mL) was added to the mixture and it was diluted with water (5 mL). The layers were separated and the organic layer was washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica gel using heptane and EtOAc as eluant giving the title compound (0.69 g, 71%). 1H NMR (CDCl3, 400 MHz) δ 9.68-9.65 (m, 1H), 6.94-6.90 (m, 2H), 3.75-3.71 (m, 2H), 2.29 (s, 3H), 2.27 (s, 6H). The ice bath was removed NaOH (2N, 5 mL) was added to the mixture and it was diluted with water (5 mL) The layers were separated the organic layer was washed with water dried over Na2SO4 evaporated The residue was purified by column chromatography on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Mesitylethanol (0.99 g, 6.0 mmol) was dissolved in DCM (10.0 mL, dry) and cooled to 0° C. 1,1,1-Tris(acetyloxy)-1λ5,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) in DCM (15 wt %, 2.80 g, 6.60 mmol) was added dropwise over a period of 20 mins. The ice bath was removed and the reaction mixture was stirred at rt for 4 h. NaOH (2N, 5 mL) was added to the mixture and it was diluted with water (5 mL). The layers were separated and the organic layer was washed with water, dried over Na2SO4, and evaporated. The residue was purified by column chromatography on silica gel using heptane and EtOAc as eluant giving the title compound (0.69 g, 71%). 1H NMR (CDCl3, 400 MHz) δ 9.68-9.65 (m, 1H), 6.94-6.90 (m, 2H), 3.75-3.71 (m, 2H), 2.29 (s, 3H), 2.27 (s, 6H). The ice bath was removed NaOH (2N, 5 mL) was added to the mixture and it was diluted with water (5 mL) The layers were separated the organic layer was washed with water dried over Na2SO4 evaporated The residue was purified by column chromatography on silica gel

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

Procedure: The title compound was prepared from [2-amino-3-(trifluoromethyl)phenyl]-(3-hydroxy-phenyl)methanone and (2,4,6-Trimethyl-phenyl)-acetaldehyde following the procedure of Example 457: MS (ES) m/z 405.9; HRMS: calcd for C25H20F3NO+H+, 408.15697; found (ESI, [M+H]+), 408.1573.

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

Procedure: A solution of dimethylsulfoxide (468 mg, 6.00 mmol) and acetonitrile (8 ml) was added to a mixture of mesitylacetoaldehyde (904 mg, 5.57 mmol), bromotrimethylsilane (919 mg, 6.00 mmol) and acetonitrile (8 ml) at 0° C. After stirring at room temperature for 0.5 hour, the mixture was diluted with water (70 ml) and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo. A mixture of the residue, 2-amino-6-(methylamino)pyrimidin-4-ol (1.69 g, 6.00 mmol), potassium carbonate (50 mg) and dimethylsulfoxide (3 ml) was heated at 100° C. for 1 hour. After cooling, the mixture was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (1:1) to give 1.07 g (68%) of the title compound. extracted with ethyl acetate (100 ml×2) washed with brine dried over sodium sulfate concentrated in vacuo was heated at 100° C. for 1 hour After cooling extracted with ethyl acetate (100 ml×2) washed with saturated aqueous sodium hydrogen carbonate and brine dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel chromatography eluting with hexane/ethyl acetate (1:1)