Reaktion #661

ord-6e943c9408c04e8290b1b5ad8908a7f2

Reaktionsgleichung

CC1(C)CCn2ncc(-c3cc(Cl)ncc3F)c2C1
CC1(C)CCn2ncc(-c3cc(
CC(C)(C)OC(=O)N[C@@H]1CCC[C@H](C(N)=O)C1
CC(C)(C)OC(=O)N[C@@H
CC1(C)CCn2ncc(-c3cc(NC(=O)[C@H]4CCC[C@@H](NC(=O)OC(C)(C)C)C4)ncc3F)c2C1
CC1(C)CCn2ncc(-c3cc(
Ausbeute 52.8%

Lösungsmittel

Reaktionsbedingungen

Temperatur
120°CELSIUS

Vorschrift

Tetrakis(triphenylphosphine)palladium(0) (0.496 g, 0.43 mmol) was added to 3-(2-chloro-5-fluoropyridin-4-yl)-5,5-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (1.2g, 4.29 mmol), tert-butyl ((1R,3S)-3-carbamoylcyclohexyl)carbamate (1.039 g, 4.29 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.496 g, 0.86 mmol) and Cesium carbonate (4.19 g, 12.87 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-((4-(5,5-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-5-fluoropyridin-2-yl)carbamoyl)cyclohexyl)carbamate (1.100 g, 52.8 %) as a white solid.

Quelle

750 AstraZeneca ELN dataset