Tert-butyl cis-(3-carbamoylcyclohexyl)carbamate → tert-butyl N-[(1R,3S)-3-[[4-(5,5-dimethyl-4,6-dihydropyrrolo[2,1-e]pyrazol-3-yl)-5-fluoro-2-pyridinyl]carbamoyl]cyclohexyl]carbamate

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Tetrakis(triphenylphosphine)palladium(0) (159 mg, 0.14 mmol) was added to 3-(2-chloro-5-fluoropyridin-4-yl)-5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (365.4 mg, 1.38 mmol), tert-butyl ((1R,3S)-3-carbamoylcyclohexyl)carbamate (333 mg, 1.38 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos) (159 mg, 0.28 mmol)and Cesium carbonate (1344 mg, 4.13 mmol) in 1,4-dioxane (15 mL). The resulting suspension was degassed for 10 minutes under nitrogen and then stirred at 120 °C for 8 hours overnight in the microwave reactor. The reaction mixture was partioned between water (30 mL) and DCM (15 mL) and seperated. _LCMS analysis showed product in the aqueous extract._ The aqueous layer was extracted with DCM (2 X 20 mL). LCMS analysis showed some product still within in the aqueous extract. _The aqueous layer was extracted again with DCM (2 X 25 mL). _ The organic extracts were combined, dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% EtOAc in heptane. Pure fractions were evaporated to dryness to afford tert-butyl ((1R,3S)-3-((4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-5-fluoropyridin-2-yl)carbamoyl)cyclohexyl)carbamate (348 mg, 53.6 %) as a white solid.

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