4-fluoro-3-(2-trimethylsilylethynyl)aniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20° C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1 N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of 3-ethynyl-4-fluoroaniline are obtained in the form of a brown oil, the characteristics of which are the following: the medium is concentrated to dryness under reduced pressure extracted three times with diethyl ether The combined organic phases are dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 460 mg of iron are added to a solution of 460 mg of [(2-fluoro-5-nitrophenyl)ethynyl](trimethyl)silane in 10 ml of methanol, and the medium is adjusted to pH 4-5 with concentrated hydrochloric acid. After refluxing for three and a half hours, the medium is cooled and then filtered through silica, and concentrated to dryness under reduced pressure. The residue is taken up with diethyl ether, the insoluble material is filtered off, and then the filtrate is concentrated to dryness under reduced pressure. 370 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline are obtained in the form of an orangey oil, the characteristics of which are the following: After refluxing for three and a half hours the medium is cooled filtered through silica concentrated to dryness under reduced pressure the insoluble material is filtered off the filtrate is concentrated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 460 mg of iron are added to a solution of 460 mg of [(2-fluoro-5-nitrophenyl)ethynyl](trimethyl)silane in 10 ml of methanol, and the medium is adjusted to pH 4-5 with concentrated hydrochloric acid. After refluxing for three and a half hours, the medium is cooled and then filtered through silica, and concentrated to dryness under reduced pressure. The residue is taken up with diethyl ether, the insoluble material is filtered off, and then the filtrate is concentrated to dryness under reduced pressure. 370 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline are obtained in the form of an orangey oil, the characteristics of which are the following: After refluxing for three and a half hours the medium is cooled filtered through silica concentrated to dryness under reduced pressure the insoluble material is filtered off the filtrate is concentrated to dryness under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In an adaption of GP 3c, 1000 mg of 4-bromo-1-methyl-1H-pyrazolo[3,4-c]pyridine (Intermediate 2.1, 4.7 mmol, 1 eq), 1590 mg 4-fluoro-3-trimethylsilanylethynyl-phenylamine (7.69 mmol, 1.63 eq.), 165 mg dichlorobis(triphenylphosphine)palladium (II) (PdCl2(PPh3)2) (0.24 mmol, 5 mol %) and 179 mg copper (I) iodide (0.94 mmol, 0.2 eq.) were dissolved in 8 mL THF (0.2 M) and treated with 16.5 mL tetra-n-butylammonium fluoride solution (1.0 M in THF, 16.5 mmol, 3.5 eq.). The resulting mixture was heated to 80° C. in a Biotage Initiator microwave oven for 30 min. Extractive work-up delivered the crude product which was used without further purification. was used without further purification

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro-6,7-dimethoxyquinazoline (500 mg, 2.23 mmol) and 3-(2′-trimethylsilylethynyl)-4-fluoroaniline (507 mg, 2.44 mmol) were refluxed in 5 mL of tert-butyl alcohol for 16 hours, cooled and filtered to afford solid (6,7-dimethoxy-quinazolin-4-yl)-(3′-ethynyl-phenyl)-amine hydrochloride which was washed with 10 mL of isopropyl alcohol and dried in vacuo at 70° C., 832 mg (83%). This was reacted in 10 mL of methanol and 1 drop of water containing 250 mg of potassium carbonate for 3 hours. The mixture was filtered and the filtrate vacuum evaoprated. This residue was triturated for 1 hour with 1N hydrochloric acid, filtered and washed with a minimum amount of water then methanol and dried in vacuo; 506 mg (63%) mp 229° C. dec. cooled filtered

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20° C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of 3-ethynyl-4-fluoroaniline are obtained in the form of a brown oil, the characteristics of which are the following: the medium is concentrated to dryness under reduced pressure extracted three times with diethyl ether The combined organic phases are dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Chloro-6,7-dimethoxyquinazoline (500 mg, 2.23 mmol) and 3-(2'-trimethylsilylethynyl)-4-fluoroaniline (507 mg, 2.44 mmol) were refluxed in 5 mL of tert-butyl alcohol for 16 hours, cooled and filtered to afford solid (6,7-dimethoxy-quinazolin-4-yl)-(3'-ethynyl-phenyl)-amine hydrochloride which was washed with 10 mL of isopropyl alcohol and dried in vacuo at 70° C., 832 mg (83%). This was reacted in 10 mL of methanol and 1 drop of water containing 250 mg of potassium carbonate for 3 hours. The mixture was filtered and the filtrate vacuum evaoprated. This residue was triturated for 1 hour with 1N hydrochloric acid, filtered and washed with a minimum amount of water then methanol and dried in vacuo; 506 mg (63%) mp 229° C. dec. cooled filtered

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20° C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1 N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of 3-ethynyl-4-fluoroaniline are obtained in the form of a brown oil, the characteristics of which are the following: the medium is concentrated to dryness under reduced pressure extracted three times with diethyl ether The combined organic phases are dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 460 mg of iron are added to a solution of 460 mg of [(2-fluoro-5-nitrophenyl)ethynyl](trimethyl)silane in 10 ml of methanol, and the medium is adjusted to pH 4-5 with concentrated hydrochloric acid. After refluxing for three and a half hours, the medium is cooled and then filtered through silica, and concentrated to dryness under reduced pressure. The residue is taken up with diethyl ether, the insoluble material is filtered off, and then the filtrate is concentrated to dryness under reduced pressure. 370 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline are obtained in the form of an orangey oil, the characteristics of which are the following: After refluxing for three and a half hours the medium is cooled filtered through silica concentrated to dryness under reduced pressure the insoluble material is filtered off the filtrate is concentrated to dryness under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In an adaption of GP 3c, 1000 mg of 4-bromo-1-methyl-1H-pyrazolo[3,4-c]pyridine (Intermediate 2.1, 4.7 mmol, 1 eq), 1590 mg 4-fluoro-3-trimethylsilanylethynyl-phenylamine (7.69 mmol, 1.63 eq.), 165 mg dichlorobis(triphenylphosphine)palladium (II) (PdCl2(PPh3)2) (0.24 mmol, 5 mol %) and 179 mg copper (I) iodide (0.94 mmol, 0.2 eq.) were dissolved in 8 mL THF (0.2 M) and treated with 16.5 mL tetra-n-butylammonium fluoride solution (1.0 M in THF, 16.5 mmol, 3.5 eq.). The resulting mixture was heated to 80° C. in a Biotage Initiator microwave oven for 30 min. Extractive work-up delivered the crude product which was used without further purification. was used without further purification