Potassium Carbonate → 8-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

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Reaction Conditions

Reaction Steps

A flask was charged with 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.50 g, 2.385 mmol, Example #3, Step C), 8-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one (0.420 g, 2.385 mmol, Astatech), K2CO3 (0.989 g, 7.16 mmol) and t-BuOH (9 mL). The flask was purged with N2 for 10 min. Pd2dba3 (0.153 g, 0.167 mmol) and X-Phos (0.159 g, 0.334 mmol) was added. The flask was again purged with N2 for 5 min and the mixture was heated to about 85° C. for about 18 h. The mixture was cooled to rt. The mixture was partitioned between DCM (200 mL) and water (200 mL) and the aqueous layer was extracted with DCM (3×100 mL). The combined organic layers were concentrated under reduced pressure. The resulting residue was suspended in EtOAc (200 mL) and trituated. The suspension was filtered and the solid was collected and washed with EtOAc (50 mL). The solid was suspended in a mixture solvents of DCM (100 mL) and MeOH (10 mL), filtered to give a gray solid, which was purified by preparative reverse phase HPLC (Table 2, method v). The fractions were collected then most of the MeCN was removed under reduced pressure, the resulting suspension was filtered and the solid was collected to give 8-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one (0.338 g, 40%): LC/MS (Table 2, Method c) Rt=1.80 min; MS m/z: 350 (M+H)+. Syk IC50=A

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