Acetonitrile → Methyl 4-amino-6'-cyclopropyl-3-fluoro-5-methoxy-[2,3'-bipyridine]-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a tube, methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (500 mg, 2.131 mmol) (˜90% pure), (6-cyclopropylpyridin-3-yl)boronic acid (417 mg, 2.56 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (78 mg, 0.107 mmol), and Cesium Fluoride (647 mg, 4.26 mmol) were charged as solids. The tube was sealed and charged with inert atmosphere. The solids were then diluted with Dioxane (5.7 ml) and Water (1.4 ml). The resulting suspension was heated to 85° C. for 18 hrs. The reaction solution was poured in to a brine solution. The aqueous phase was extracted with EtOAc (3×25 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under vacuum. The product was purified (flash chromatography: silica, 5-50% EtOAc in Hex 16 CV; C18 5-100% ACN in H2O 16 CV) to yield methyl 4-amino-6′-cyclopropyl-3-fluoro-5-methoxy-[2,3′-bipyridine]-6-carboxylate (0.218 g, 0.687 mmol, 32.2% yield). ESIMS for m/z 318 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 0.99 (tt, J=7.6, 2.7 Hz, 4H), 2.17 (tt, J=7.8, 5.1 Hz, 1H), 3.77 (s, 3H), 3.86 (s, 3H), 6.55 (s, 2H), 7.42 (d, J=8.9 Hz, 1H), 8.00 (ddd, J=8.2, 2.3, 1.2 Hz, 1H), 8.77 (t, J=2.0 Hz, 1H). 19F NMR (376 MHz, DMSO-d6) δ −141.19.

Provenance & Evidence