Cesium carbonate → US9777003, Example 66

Participants

Reaction Conditions

Reaction Steps

1-Benzyl-5-chloro-2-(1,3-thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridine (32 mg, 0.098 mmol, from Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (27 mg, 0.12 mmol) and Cs2CO3 (32 mg, 0.098 mmol) were combined in toluene (3.0 mL) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (7.7 mg, 0.0098 mmol) was added. The mixture was degassed by a stream of nitrogen through the solution for 10 minutes. The reaction was heated to 108° C. overnight. Additional di-tert-butyl hydrazine-1,2-dicarboxylate (23 mg, 0.098 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (7.7 mg, 0.0098 mmol) were added. The reaction was heated to 110° C. over a second night. The mixture was partitioned between EtOAc and water, extracted three times, and the combined extracts were dried over sodium sulfate, filtered and concentrated. The intermediate di-tert-butyl 1-[1-benzyl-2-(1,3-thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate was purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH) and the eluent was evaporated. The product was dissolved in AcOH (0.60 mL) and was heated in the microwave to a temperature of 156° C. for 5 minutes. The AcOH was removed in vacuo and the sample was reconstituted and purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN and H2O containing 0.15% NH4OH). Yield: (1.0 mg, 2.9%).

Provenance & Evidence