反应详情

温度

108 °C

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%).

1. customThe mixture was degassed by a stream of nitrogen through the solution for 10 minutes
2. temperatureThe reaction was heated to 110° C. over a second night
3. customThe mixture was partitioned between EtOAc and water
4. extractionextracted three times
5. dry with materialthe combined extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe 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
9. washeluting with a gradient of MeCN and H2O containing 0.15% NH4OH) and the eluent
10. customwas evaporated
11. dissolutionThe product was dissolved in AcOH (0.60 mL)
12. temperaturewas heated in the microwave to a temperature of 156° C. for 5 minutes
13. customThe AcOH was removed in vacuo
14. custompurified via preparative HPLC-MS (C18
15. washeluting with a gradient of MeCN and H2O containing 0.15% NH4OH)