4-methoxybut-2-yn-1-ol

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: To a mixture of 300 mg of 4-tert.-butyl-N-[6-chloro-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide (Example 12c) and 1.8 g of 4-methoxy-2-butyn-1-ol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) was added 288 mg of 55% NaH in mineral oil. After evolution of gas had ceased, the brown suspension was stirred at room temperature for 24 h. Another 288 mg of 55% NaH in mineral oil was added and the mixture was stirred at 60° C. for 18 h. The mixture was cooled, diluted with 50 ml of 10% aqueous citric acid and extracted 4 times with 50 ml of ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with hexane:ethyl acetate 1:1 and precipitated from diethyl ether to give 213 mg of 4-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide as a white powder. LC-MS: tR=5.61 min, [M+1]+=480.30, [M−1]−=478.39. prepared the mixture was stirred at 60° C. for 18 h The mixture was cooled extracted 4 times with 50 ml of ethyl acetate The combined organic phases were washed with water dried over MgSO4 evaporated The crude product was purified by column chromatography on silica gel eluting with hexane:ethyl acetate 1:1 precipitated from diethyl ether

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

Procedure: To a mixture of 250 mg of 4-tert.-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimi-dinyl]benzene sulfonamide (Example 5a) and 1.11 g of 4-methoxy-2-butynol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) in 15 ml THF was added 177 mg of 55% NaH in mineral oil. The suspension was stirred for 16 h at reflux. The reaction mixture was cooled, diluted with 100 ml 10% aqueous citric acid and extracted 4 times with 50 ml of ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated. The crude product was purified by chromatography on prep. tlc-plates with ethyl acetate:methanol:sat. aqueous ammonia 8:2:1 to give 116 mg of 4-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(o-methoxy-phenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide as a slightly yellow foam. LC-MS: tR=5.19 min, [M+1]+=590.40, [M−1]−=588.39 prepared at reflux The reaction mixture was cooled extracted 4 times with 50 ml of ethyl acetate The combined organic phases were washed with water dried over MgSO4 evaporated The crude product was purified by chromatography on prep

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

Procedure: To a solution of 300 mg of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)4-pyrimidinyl]-2-pyridine sulfonamide (Example 1f) and 1.47 g of 4-methoxy-2-butynol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) in 15 ml of DMF was carefully added 234 mg of 55% NaH in mineral oil. The brown solution stirred for 24 h at room temperature before further 120 mg of 55% NaH in mineral oil was added. Stirring was continued for 24 h. The mixture was diluted with 100 ml of 10% aqueous citric acid and extracted four times with 50 ml of ethyl acetate. The combined organic phases were washed twice with 50 ml of water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with ethyl acetate to give 154 mg of 5-isopropyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide as a yellow solid. LC-MS: tR=4.84 min, [M+1]+=576.42, [M−1]−=574.37. was added extracted four times with 50 ml of ethyl acetate The combined organic phases were washed twice with 50 ml of water dried over MgSO4 evaporated The crude product was purified by column chromatography on silica gel eluting with ethyl acetate