1-fluoro-2-[isocyano-(4-methylphenyl)sulfonylmethyl]benzene

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

Procedure: A solution of 2-(sec-butylamino)thiazolo[5,4-b]pyridine-5-carbaldehyde (presumed 0.24 mmol, 1.0 eq.) and concentrated aqueous NH4OH (0.050 mL) in THF (0.8 mL) was stirred overnight. 1-Fluoro-2-(isocyano(tosyl)methyl)benzene (0.0841 g, 0.291 mmol, 1.2 eq.) and piperazine (0.0394 g, 0.457 mmol, 1.9 eq.) were added, and the reaction mixture was stirred overnight. It was then diluted with EtOAc and washed with water, saturated aqueous NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with CH2Cl2 (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give N-sec-butyl-5-(4-(2-fluorophenyl)-1H-imidazol-5-yl)thiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.0228 g, 26% yield). LC/MS (MH)=368.23. washed with water, saturated aqueous NaHCO3, and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with CH2Cl2 (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(sec-butylamino)thiazolo[5,4-b]pyridine-5-carbaldehyde (presumed 0.24 mmol, 1.0 eq.), 1-fluoro-2-(isocyano(tosyl)methyl)benzene (0.0874 g, 0.302 mmol, 1.3 eq.), and K2CO3 (0.0654 g, 0.473 mmol, 2.0 eq.) in EtOH (2.4 mL) was refluxed overnight. After cooling to room temperature, the reaction mixture was concentrated in vacuo, and the residue was taken up in EtOAc and water. After separation of the layers, the organic layer was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give N-sec-butyl-5-(4-(2-fluorophenyl)oxazol-5-yl)thiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.0264 g, 30% yield). LC/MS (MH)=369.20. the reaction mixture was concentrated in vacuo After separation of the layers the organic layer was washed with saturated aqueous NaHCO3 and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with EtOAc (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(isopropylamino)thiazolo[4,5-c]pyridine-6-carbaldehyde (example 10, step 4) (presumed 0.244 mmol, 1.0 eq.) and concentrated aqueous NH4OH (0.050 mL) in THF (1 mL) was stirred overnight. 1-Fluoro-2-(isocyano(tosyl)methyl)benzene (0.0880 g, 0.304 mmol, 1.2 eq.) and piperazine (0.0371 g, 0.431 mmol, 1.8 eq.) were added, and the reaction mixture was stirred overnight. It was then diluted with EtOAc and washed with water, saturated aqueous NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give 6-(4-(2-fluorophenyl)-1H-imidazol-5-yl)-N-isopropylthiazolo[4,5-c]pyridin-2-amine as a light orange solid (0.0212 g, 25% yield). LC/MS (MH)=354.18. washed with water, saturated aqueous NaHCO3, and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with EtOAc (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(isopropylamino)thiazolo[4,5-c]pyridine-6-carbaldehyde (presumed 0.234 mmol, 1.0 eq.), 1-fluoro-2-(isocyano(tosyl)methyl)benzene (0.079 g, 0.273 mmol, 1.2 eq.), and K2CO3 (0.0654 g, 0.473 mmol, 2.0 eq.) in EtOH (2.4 mL) was refluxed for 4.75 hr. After cooling to room temperature, the reaction mixture was concentrated in vacuo, and the residue was taken up in EtOAc and water. After separation of the layers, the organic layer was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give 6-(4-(2-fluorophenyl)oxazol-5-yl)-N-isopropylthiazolo[4,5-c]pyridin-2-amine as a light yellow solid (0.0243 g, 29% yield). LC/MS (MH)=355.16. the reaction mixture was concentrated in vacuo After separation of the layers the organic layer was washed with saturated aqueous NaHCO3 and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with EtOAc (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(sec-butylamino)thiazolo[5,4-b]pyridine-5-carbaldehyde (presumed 0.24 mmol, 1.0 eq.) and concentrated aqueous NH4OH (0.050 mL) in THF (0.8 mL) was stirred overnight. 1-Fluoro-2-(isocyano(tosyl)methyl)benzene (0.0841 g, 0.291 mmol, 1.2 eq.) and piperazine (0.0394 g, 0.457 mmol, 1.9 eq.) were added, and the reaction mixture was stirred overnight. It was then diluted with EtOAc and washed with water, saturated aqueous NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with CH2Cl2 (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give N-sec-butyl-5-(4-(2-fluorophenyl)-1H-imidazol-5-yl)thiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.0228 g, 26% yield). LC/MS (MH)=368.23. washed with water, saturated aqueous NaHCO3, and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with CH2Cl2 (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(sec-butylamino)thiazolo[5,4-b]pyridine-5-carbaldehyde (presumed 0.24 mmol, 1.0 eq.), 1-fluoro-2-(isocyano(tosyl)methyl)benzene (0.0874 g, 0.302 mmol, 1.3 eq.), and K2CO3 (0.0654 g, 0.473 mmol, 2.0 eq.) in EtOH (2.4 mL) was refluxed overnight. After cooling to room temperature, the reaction mixture was concentrated in vacuo, and the residue was taken up in EtOAc and water. After separation of the layers, the organic layer was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give N-sec-butyl-5-(4-(2-fluorophenyl)oxazol-5-yl)thiazolo[5,4-b]pyridin-2-amine as a yellow solid (0.0264 g, 30% yield). LC/MS (MH)=369.20. the reaction mixture was concentrated in vacuo After separation of the layers the organic layer was washed with saturated aqueous NaHCO3 and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with EtOAc (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(isopropylamino)thiazolo[4,5-c]pyridine-6-carbaldehyde (example 10, step 4) (presumed 0.244 mmol, 1.0 eq.) and concentrated aqueous NH4OH (0.050 mL) in THF (1 mL) was stirred overnight. 1-Fluoro-2-(isocyano(tosyl)methyl)benzene (0.0880 g, 0.304 mmol, 1.2 eq.) and piperazine (0.0371 g, 0.431 mmol, 1.8 eq.) were added, and the reaction mixture was stirred overnight. It was then diluted with EtOAc and washed with water, saturated aqueous NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give 6-(4-(2-fluorophenyl)-1H-imidazol-5-yl)-N-isopropylthiazolo[4,5-c]pyridin-2-amine as a light orange solid (0.0212 g, 25% yield). LC/MS (MH)=354.18. washed with water, saturated aqueous NaHCO3, and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with EtOAc (3×) dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: A solution of 2-(isopropylamino)thiazolo[4,5-c]pyridine-6-carbaldehyde (presumed 0.234 mmol, 1.0 eq.), 1-fluoro-2-(isocyano(tosyl)methyl)benzene (0.079 g, 0.273 mmol, 1.2 eq.), and K2CO3 (0.0654 g, 0.473 mmol, 2.0 eq.) in EtOH (2.4 mL) was refluxed for 4.75 hr. After cooling to room temperature, the reaction mixture was concentrated in vacuo, and the residue was taken up in EtOAc and water. After separation of the layers, the organic layer was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated in vacuo. MeOH was added to the residue, and the mixture was subjected to autoprep. The appropriate fractions were collected, and NaHCO3 (s) was added. The solution was then concentrated in vacuo not to dryness and extracted with EtOAc (3×). The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo to give 6-(4-(2-fluorophenyl)oxazol-5-yl)-N-isopropylthiazolo[4,5-c]pyridin-2-amine as a light yellow solid (0.0243 g, 29% yield). LC/MS (MH)=355.16. the reaction mixture was concentrated in vacuo After separation of the layers the organic layer was washed with saturated aqueous NaHCO3 and brine dried over Na2SO4 filtered concentrated in vacuo MeOH was added to the residue The appropriate fractions were collected NaHCO3 (s) was added The solution was then concentrated in vacuo not to dryness extracted with EtOAc (3×) dried over Na2SO4 filtered concentrated in vacuo