7-amino-3-methyl-3,4-dihydro-1H-quinolin-2-one

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

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

Procedure: A flask was charged with 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.38 g, 1.8 mmol, Example #3, Step C), 7-amino-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.30 g, 1.7 mmol), K2CO3 (0.38 g, 2.7 mmol), Pd2dba3 (0.17 g, 0.18 mmol) and X-Phos (0.17 g, 0.36 mmol) in 1,4-dioxane (20 mL). The flask was evacuated and purged with N2 (3×), and the mixture was heated to about 100° C. overnight. The mixture was cooled to rt and concentrated under reduced pressure to a residue. The residue was purified by preparative TLC (1.0 mm plate), eluting with DCM/MeOH (12:1). The product obtained was further purified by preparative HPLC (Table 2, Method r) to give 7-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.15 g, 24%): LC/MS (Table 2, Method g) Rt=1.04 min; MS m/z: 177 (M+H)+. Syk IC50=A The flask was evacuated purged with N2 (3×) The mixture was cooled to rt concentrated under reduced pressure to a residue The residue was purified by preparative TLC (1.0 mm plate) eluting with DCM/MeOH (12:1) The product obtained was further purified by preparative HPLC (Table 2, Method r)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with methyl 3-(2,4-dinitrophenyl)-2-methylpropanoate (1.1 g, 4.1 mmol), 10 wt % Pd on carbon (0.25 g, 2.3 mmol), and t-BuOH (15 mL). The mixture was degassed with H2 three times and was stirred for about 72 h at about 50° C. The mixture was filtered and the filtrate was concentrated under reduced pressure to give 7-amino-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.70 g, 92%): LC/MS (Table 2, Method g) Rt=1.04 min; MS m/z: 177 (M+H)+. The mixture was degassed with H2 three times The mixture was filtered the filtrate was concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with methyl 3-(2,4-dinitrophenyl)-2-methylpropanoate (1.1 g, 4.1 mmol), 10 wt % Pd on carbon (0.25 g, 2.3 mmol), and t-BuOH (15 mL). The mixture was degassed with H2 three times and was stirred for about 72 h at about 50° C. The mixture was filtered and the filtrate was concentrated under reduced pressure to give 7-amino-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.70 g, 92%): LC/MS (Table 2, Method g) Rt=1.04 min; MS m/z: 177 (M+H)+. The mixture was degassed with H2 three times The mixture was filtered the filtrate was concentrated under reduced pressure

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

Procedure: A flask was charged with 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.38 g, 1.8 mmol, Example #3, Step C), 7-amino-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.30 g, 1.7 mmol), K2CO3 (0.38 g, 2.7 mmol), Pd2dba3 (0.17 g, 0.18 mmol) and X-Phos (0.17 g, 0.36 mmol) in 1,4-dioxane (20 mL). The flask was evacuated and purged with N2 (3×), and the mixture was heated to about 100° C. overnight. The mixture was cooled to rt and concentrated under reduced pressure to a residue. The residue was purified by preparative TLC (1.0 mm plate), eluting with DCM/MeOH (12:1). The product obtained was further purified by preparative HPLC (Table 2, Method r) to give 7-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.15 g, 24%): LC/MS (Table 2, Method g) Rt=1.04 min; MS m/z: 177 (M+H)+. Syk IC50=A The flask was evacuated purged with N2 (3×) The mixture was cooled to rt concentrated under reduced pressure to a residue The residue was purified by preparative TLC (1.0 mm plate) eluting with DCM/MeOH (12:1) The product obtained was further purified by preparative HPLC (Table 2, Method r)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with methyl 3-(2,4-dinitrophenyl)-2-methylpropanoate (1.1 g, 4.1 mmol), 10 wt % Pd on carbon (0.25 g, 2.3 mmol), and t-BuOH (15 mL). The mixture was degassed with H2 three times and was stirred for about 72 h at about 50° C. The mixture was filtered and the filtrate was concentrated under reduced pressure to give 7-amino-3-methyl-3,4-dihydroquinolin-2(1H)-one (0.70 g, 92%): LC/MS (Table 2, Method g) Rt=1.04 min; MS m/z: 177 (M+H)+. The mixture was degassed with H2 three times The mixture was filtered the filtrate was concentrated under reduced pressure