Reaktion #613

ord-5545e57a105549059abb855326d6ce2b

Reaktionsgleichung

Fc1cnc(Cl)cc1-c1cnn2c1CCCCC2
Fc1cnc(Cl)cc1-c1cnn2
CC(C)(C)OC(=O)N[C@@H]1CCC[C@H](C(N)=O)C1
CC(C)(C)OC(=O)N[C@@H
CC(C)(C)OC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCCC4)c(F)cn2)C1
CC(C)(C)OC(=O)N[C@@H
Ausbeute 72.4%

Lösungsmittel

Reaktionsbedingungen

Temperatur
120°CELSIUS

Vorschrift

Tetrakis(triphenylphosphine)palladium(0) (0.304 g, 0.26 mmol) was added to 3-(2-chloro-5-fluoropyridin-4-yl)-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepine (0.700 g, 2.63 mmol), tert-butyl ((1R,3S)-3-carbamoylcyclohexyl)carbamate (0.638 g, 2.63 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.305 g, 0.53 mmol) and Cesium carbonate (2.58 g, 7.90 mmol) in 1,4-dioxane (10 mL)Degassed for 5 mins under nitrogen and the resulting suspension was stirred at 120 °C for 17 hours in the microwave reactor. The reaction mixture was partitioned between water (20ml) and ethyl acetate (100ml) filtered and separated. The organics were absorbed onto silica and purified by flash silica chromatography, elution gradient 1:1 EtOAc in heptane. Pure fractions were evaporated to dryness to afford tert-butyl ((1R,3S)-3-((5-fluoro-4-(5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl)pyridin-2-yl)carbamoyl)cyclohexyl)carbamate (0.900 g, 72.4 %) as a white solid. Product is crude so used directly in the next step.

Quelle

750 AstraZeneca ELN dataset