N-ethyl-N-methylformamide

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: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (349 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.37 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-4-methyl-pyridin-3-ylamine (605 mg) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:1 (v:v) gives 0.67 g of the compound as a brownish oil. Under stirring phosphorous oxide chloride (0.37 ml) is added dropwise by syringe is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 1 hour to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:1 (v:v)

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (349 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.37 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-4-methyl-pyridin-3-ylamine (605 mg) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:1 (v:v) gives 0.67 g of the compound as a brownish oil. Under stirring phosphorous oxide chloride (0.37 ml) is added dropwise by syringe is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 1 hour to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:1 (v:v)

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour. To this solution, 6-(2,4-Dichloro-phenoxy)-pyridin-3-ylamine (0.5 g) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification by flash chromatography over silica gel with hexane/ethyl acetate 3:4 (v:v) gives 0.31 g of the compound as a yellow oil. Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 1 hour to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification by flash chromatography over silica gel with hexane/ethyl acetate 3:4 (v:v)

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour. To this solution, 6-(2,4-Dichloro-phenoxy)-pyridin-3-ylamine (0.5 g) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification by flash chromatography over silica gel with hexane/ethyl acetate 3:4 (v:v) gives 0.31 g of the compound as a yellow oil. Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 1 hour to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification by flash chromatography over silica gel with hexane/ethyl acetate 3:4 (v:v)

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 0.5 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(3-tert-butyl-phenoxy)-5-methyl-pyridin-3-ylamine (0.51 g) dissolved in 5.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 2 hours. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with ethyl acetate gives 0.56 g of the compound as a brown oil. Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 2 hours to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification of this gum by flash chromatography over silica gel with ethyl acetate

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 0.5 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(3-tert-butyl-phenoxy)-5-methyl-pyridin-3-ylamine (0.51 g) dissolved in 5.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 2 hours. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with ethyl acetate gives 0.56 g of the compound as a brown oil. Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 2 hours to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification of this gum by flash chromatography over silica gel with ethyl acetate

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-ylamine (0.6 g) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:2 (v:v) gives 0.52 g of the compound as a yellow oil. Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 1 hour to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:2 (v:v)

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

Procedure: In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-ylamine (0.6 g) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:2 (v:v) gives 0.52 g of the compound as a yellow oil. Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at an ambient temperature for 1 hour to get a pH of about 11 stirring is continued for 10 minutes The mixture is then extracted with dichloromethane (2×50 ml) The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:2 (v:v)

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

Procedure: In a 10 ml single-necked round-bottomed flask, 3.1 mg of ethylmethylformamide is solubilized in 0.25 ml of dry dichloromethane at ambient temperature (colourless solution). Under stirring, 0.0032 ml of phosphorous oxide chloride is added dropwise by syringe. Stirring at ambient temperature is continued for 1.0 hour, whereupon a pink-orange solution is obtained. To this solution, 7.0 mg of 6-(4-chloro-3-trifluoromethyl-phenoxy)-2-methyl-5-trimethylsilanylethynyl-pyridin-3-ylamine dissolved in 0.75 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at room temperature for 2.5 hours. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 15 minutes. The mixture is then extracted with two 10 ml portions of diethyl ether. The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo to obtain 6.0 mg of the compound as a yellow oil. RP HPLC: retention time of compound: 1.61 minutes. Stirring at ambient temperature is obtained is added dropwise by syringe giving a yellow solution Stirring is continued at room temperature for 2.5 hours to get a pH of about 11 stirring is continued for 15 minutes The mixture is then extracted with two 10 ml portions of diethyl ether The combined organic phases are then dried over sodium sulfate filtered the solvent is removed in vacuo