N',N'-dimethylbut-2-yne-1,4-diamine

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

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

Procedure: Prepared analogously to 35.3 from 0.080 g 4-[2-(trans-3-acetylamino-cyclobutoxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid (cpd. 35.2) and 0.045 g 4-(dimethylamino)-but-2-ynylamin*2HCl.

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: A solution of methyl benzoylformate (0.50 g) and 4-dimethylamino-2-butynylamine (0.38 g) in methanol (5 ml) was refluxed for 3 hours. To the reaction mixture was added 1N aqueous solution of sodium hydroxide and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (20:1) as an eluent to give N-(4-dimethylamino-2-butynyl)benzoylformamide (0.39 g). the mixture was extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (20:1) as an eluent

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

Procedure: A mixture of (S)-(+)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid (1.13 g, 80% ee) and N,N'-carbonyldiimidazole (0.77 g) in chloroform (5 ml) was stirred at room temperature for 2 hours. After an addition of 4-dimethylamino-2-butynylamine (0.54 g), the mixture was stirred at the same temperature for an additional hour, then the mixture was poured into water, and extracted with ethyl acetate. The extract was washed with water and the organic layer was extracted with 1N-hydrochloric acid. The acidic solution was adjusted to pH 13 with aqueous solution of sodium hydroxide and extracted with ethyl acetate. The extract was washed with sodium chloride aqueous solution, dried over sodium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (10:1) as an eluent to give (-)-N-(4-dimethylamino-2-butynyl)-2-cyclohexyl-2-hydroxy-2-phenylacetamide (0.60 g, 88% ee). the mixture was stirred at the same temperature for an additional hour extracted with ethyl acetate The extract was washed with water the organic layer was extracted with 1N-hydrochloric acid extracted with ethyl acetate The extract was washed with sodium chloride aqueous solution dried over sodium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (10:1) as an eluent

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

Procedure: A mixture of (S)-(+)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid (1.13 g, 80% ee) and N,N'-carbonyldiimidazole (0.77 g) in chloroform (5 ml) was stirred at room temperature for 2 hours. After an addition of 4-dimethylamino-2-butynylamine (0.54 g), the mixture was stirred at the same temperature for an additional hour, then the mixture was poured into water, and extracted with ethyl acetate. The extract was washed with water and the organic layer was extracted with 1N-hydrochloric acid. The acidic solution was adjusted to pH 13 with aqueous solution of sodium hydroxide and extracted with ethyl acetate. The extract was washed with sodium chloride aqueous solution, dried over sodium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (10:1) as an eluent to give (-)-N-(4-dimethylamino-2-butynyl)-2-cyclohexyl-2-hydroxy-2-phenylacetamide (0.60 g, 88% ee). the mixture was stirred at the same temperature for an additional hour extracted with ethyl acetate The extract was washed with water the organic layer was extracted with 1N-hydrochloric acid extracted with ethyl acetate The extract was washed with sodium chloride aqueous solution dried over sodium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (10:1) as an eluent

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

Procedure: Prepared analogously to 35.3 from 0.080 g 4-[2-(trans-3-acetylamino-cyclobutoxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid (cpd. 35.2) and 0.045 g 4-(dimethylamino)-but-2-ynylamin*2HCl.

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

Procedure: Prepared analogously to 35.3 from 0.080 g 4-[2-(trans-3-acetylamino-cyclobutoxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid (cpd. 35.2) and 0.045 g 4-(dimethylamino)-but-2-ynylamin*2HCl.

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

Procedure: A solution of methyl benzoylformate (0.50 g) and 4-dimethylamino-2-butynylamine (0.38 g) in methanol (5 ml) was refluxed for 3 hours. To the reaction mixture was added 1N aqueous solution of sodium hydroxide and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (20:1) as an eluent to give N-(4-dimethylamino-2-butynyl)benzoylformamide (0.39 g). the mixture was extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (20:1) as an eluent

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

Procedure: A mixture of (S)-(+)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid (1.13 g, 80% ee) and N,N'-carbonyldiimidazole (0.77 g) in chloroform (5 ml) was stirred at room temperature for 2 hours. After an addition of 4-dimethylamino-2-butynylamine (0.54 g), the mixture was stirred at the same temperature for an additional hour, then the mixture was poured into water, and extracted with ethyl acetate. The extract was washed with water and the organic layer was extracted with 1N-hydrochloric acid. The acidic solution was adjusted to pH 13 with aqueous solution of sodium hydroxide and extracted with ethyl acetate. The extract was washed with sodium chloride aqueous solution, dried over sodium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (10:1) as an eluent to give (-)-N-(4-dimethylamino-2-butynyl)-2-cyclohexyl-2-hydroxy-2-phenylacetamide (0.60 g, 88% ee). the mixture was stirred at the same temperature for an additional hour extracted with ethyl acetate The extract was washed with water the organic layer was extracted with 1N-hydrochloric acid extracted with ethyl acetate The extract was washed with sodium chloride aqueous solution dried over sodium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (10:1) as an eluent

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

Procedure: A solution of methyl benzoylformate (0.50 g) and 4-dimethylamino-2-butynylamine (0.38 g) in methanol (5 ml) was refluxed for 3 hours. To the reaction mixture was added 1N aqueous solution of sodium hydroxide and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (20:1) as an eluent to give N-(4-dimethylamino-2-butynyl)benzoylformamide (0.39 g). the mixture was extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with a mixture of chloroform and methanol (20:1) as an eluent