N-(4-aminophenyl)prop-2-enamide

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a slurry of (1-benzyl-1H-indazol-5-yl)-(4-chloro-[1,3,5]triazin-2-yl)-amine (Example 3, Step 3) (80.0 mg, 0.238 mmol) in IpOH (3.0 ml) was added DIEA (0.062 mL, 0.356 mmol) and N-(4-aminophenyl)acrylamide (Example 2, Step 2) (42.4 mg, 0.261 mmol). The mix was heated at 100° C. for 18 h. The solution was then cooled to RT. A precipitate fells out of solution, was filtered off and dried under reduced pressure to give N-{4-[4-(1-benzyl-1H-indazol-5-ylamino)-[1,3,5]triazin-2-ylamino]-phenyl}-acrylamide: MS m/z=463[M+H]+. Calc'd for C26H22N8O: 462.19. The solution was then cooled to RT was filtered off dried under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a slurry of (4-chloro-[1,3,5]triazin-2-yl)-(3,4,5-trimethoxy-phenyl)amine (29.9 mg, 0.101 mmol) in IpOH (2.5 ml) was added DIEA (0.026 mL, 0.151 mmol) and N-(4-aminophenyl)acrylamide (Step 2) (18 mg, 0.111 mmol). The mixture was heated at 100° C. for 18 h. The solution was cooled to RT. The organics were evaporated in vacuo and the residue was purified by column chromatography using 9:1 CH2Cl2/MeOH as the solvent to give N-(4-[4-(3,4,5-trimethoxy-phenylamino)-[1,3,5]triazin-2-ylamino]phenyl}-acrylamide: MS m/z 423[M+H]+. Calc'd for C21H22N6O4: 422.17. The solution was cooled to RT The organics were evaporated in vacuo the residue was purified by column chromatography

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

Procedure: A mixture of N-(4-nitrophenyl)-acrylamide (Step 1) (0.203 g, 1.06 mmol), Iron powder (0.354 g, 6.34 mmol), FeSO4 (0.587 g, 2.11 mmol), Celite® (0.2 g) and water (6 mL) was heated to reflux with stirring for 3 h. The reaction mixture was cooled to RT and the solution was made basic to pH 13-14 by the addition of 2 N NaOH. The reaction mixture was diluted with EtOAc and water. The solution was filtered to remove the solids and solids washed with EtOAc. The aqueous layer was extracted three times with EtOAc (25 mL) and the combined organics were dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography using EtOAc as the solvent to give N-(4-aminophenyl)-acrylamide. was heated to reflux The solution was filtered to remove the solids and solids washed with EtOAc The aqueous layer was extracted three times with EtOAc (25 mL) the combined organics were dried over Na2SO4 filtered evaporated in vacuo The residue was purified by column chromatography