4-(chloromethyl)-2-methoxy-1-phenylmethoxybenzene

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: To a mixture of ethyl 3-(3-ethoxy-1H-pyrazol-4-yl)propionate (1.59 g), 4-benzyloxy-3-methoxybenzyl chloride (1.97 g), and N,N-dimethylformamide (30 ml), sodium hydride (60%, oily, 0.30 g) was added at 0° C., and then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then, with saturated aqueous sodium chloride solution, and dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[1-(4-benzyloxy-3-methoxybenzyl)-3-ethoxy-1H-pyrazol-4-yl]propionate (2.93 g, yield: 89%) was obtained as a colorless oily substance from the fractions eluted with ethyl acetate-hexane (1:2, volume ratio). was added at 0° C. was extracted with ethyl acetate The ethyl acetate layer was washed with water with saturated aqueous sodium chloride solution, and dried (MgSO4) concentrated

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

Procedure: To a mixture of ethyl 3-(3-ethoxy-1H-pyrazol-4-yl)propionate (1.59 g), 4-benzyloxy-3-methoxybenzyl chloride (1.97 g), and N,N-dimethylformamide (30 ml), sodium hydride (60%, oily, 0.30 g) was added at 0° C., and then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then, with saturated aqueous sodium chloride solution, and dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[1-(4-benzyloxy-3-methoxybenzyl)-3-ethoxy-1H-pyrazol-4-yl]propionate (2.93 g, yield: 89%) was obtained as a colorless oily substance from the fractions eluted with ethyl acetate-hexane (1:2, volume ratio). was added at 0° C. was extracted with ethyl acetate The ethyl acetate layer was washed with water with saturated aqueous sodium chloride solution, and dried (MgSO4) concentrated

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

Procedure: To a mixture of ethyl 3-(3-ethoxy-1H-pyrazol-4-yl)propionate (1.59 g), 4-benzyloxy-3-methoxybenzyl chloride (1.97 g), and N,N-dimethylformamide (30 ml), sodium hydride (60%, oily, 0.30 g) was added at 0° C., and then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then, with saturated aqueous sodium chloride solution, and dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[1-(4-benzyloxy-3-methoxybenzyl)-3-ethoxy-1H-pyrazol-4-yl]propionate (2.93 g, yield: 89%) was obtained as a colorless oily substance from the fractions eluted with ethyl acetate-hexane (1:2, volume ratio). was added at 0° C. was extracted with ethyl acetate The ethyl acetate layer was washed with water with saturated aqueous sodium chloride solution, and dried (MgSO4) concentrated

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: In analogy to the method described in example A1, 3.67 g (22.8 mmol) of 4-amino-5-chloro-2,6-dimethylpyrimidine, 6.0 g (22.8 mmol) of 4-benzyloxy-3-methoxybenzyl chloride and 0.91 g (23 mmol) of sodium hydride (60% suspension in liquid paraffin) are reacted in a total of 190 ml of N-methylpyrrolidone. After chromatography on silica gel (mobile phase: toluene/dioxane=10:1) and crystallization from petroleum ether, the title compound is isolated as a pale beige solid. Yield: 3.42 g (39% of theory). m.p.: 101-105° C. After chromatography on silica gel (mobile phase: toluene/dioxane=10:1) and crystallization from petroleum ether

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, a mixture of sodium hydroxide (1.43 g, 35.85 mmol) and tetrabutylammonium iodide (0.30 g, 0.82 mmol) in 8 ml benzene and 2.8 ml H2O was heated at 70° C. to form a homogeneous mixture. A mixture of the product of Step 1 (8.05 g, 30.64 mmol) and isobutraaldehyde (2.95 g, 40.85 mmol) in 20 ml benzene was added to the above solution dropwise. The resulting reaction mixture was heated at 70-75° C. for 6 h. The product was extracted with ethyl acetate and washed with H2O. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried with MgSO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to yield a colorless oil in 8.32 g. NMR spectra of the product were consistent for the proposed structure. to form a homogeneous mixture was added to the above solution dropwise The resulting reaction mixture was heated at 70-75° C. for 6 h The product was extracted with ethyl acetate washed with H2O The aqueous layer was extracted with ethyl acetate The combined organic layer was washed with brine dried with MgSO4 concentrated The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/9) to yield a colorless oil in 8.32 g

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

Procedure: Thionyl chloride (5.95 g, 50.0 mmol) was added to a mixture of 4-benzyloxy-3-methoxybenzylalcohol (10.0 g, 40.9 mmol) in 50 ml ether at room temperature. The reaction turned into a clear solution and was monitored by TLC. The reaction was quenched with H2O. The product was extracted with ether. The aqueous layer was extracted with ether. The combined organic layer washed with 5% NaHCO3, brine and dried with Na2SO4. Ether was evaporated and the residue was purified by chromatography (on silica gel, ethyl acetate/hexane=2/8) to give a white solid 8.10 g. NMR spectra of the product were consistent for the proposed structure. The reaction was quenched with H2O The product was extracted with ether The aqueous layer was extracted with ether The combined organic layer washed with 5% NaHCO3, brine dried with Na2SO4 Ether was evaporated the residue was purified by chromatography (on silica gel, ethyl acetate/hexane=2/8)

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

Procedure: To a mixture of ethyl 3-(3-ethoxy-1H-pyrazol-4-yl)propionate (1.59 g), 4-benzyloxy-3-methoxybenzyl chloride (1.97 g), and N,N-dimethylformamide (30 ml), sodium hydride (60%, oily, 0.30 g) was added at 0° C., and then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then, with saturated aqueous sodium chloride solution, and dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[1-(4-benzyloxy-3-methoxybenzyl)-3-ethoxy-1H-pyrazol-4-yl]propionate (2.93 g, yield: 89%) was obtained as a colorless oily substance from the fractions eluted with ethyl acetate-hexane (1:2, volume ratio). was added at 0° C. was extracted with ethyl acetate The ethyl acetate layer was washed with water with saturated aqueous sodium chloride solution, and dried (MgSO4) concentrated