3-Aminopyridine → 1-(2-(2-(5-Chloro-2-(pyridin-3-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

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Reaction Conditions

Reaction Steps

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide (A14) (100 mg, 297 μmol), Cs2CO3 (291 mg, 892 μmol) and 3-aminopyridine (56.0 mg, 595 μmol) in 1,4-dioxane (2.0 mL) was sonicated for 10 minutes. To this Xantphos (6.88 mg, 11.9 μmol) and Pd(OAc)2 (1.33 mg, 5.95 μmol) were added and the resulting mixture heated under microwave irradiation for 20 minutes at 120° C. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-50% MeOH in EtOAc) to yield a tan solid. This was sonicated for 10 min in water (50 mL) and filtered to give the title compound 6 as a green solid (29 mg, 25%); 1H NMR (400 MHz, CDCl3) δ 8.80-8.74 (d, J=2.5 Hz, 1H), 8.33 (s, 1H), 8.32-8.28 (dd, J=4.7, 1.3 Hz, 1H), 8.18-8.12 (m, 1H), 7.47-7.42 (d, J=7.2 Hz, 1H), 7.38-7.34 (m, 3H), 7.34-7.25 (m, 2H), 5.56 (s, 1H), 5.37 (s, 1H), 3.34-3.14 (m, 4H), 1.78 (s, 2H), 1.16 (s, 2H). LCMS-A: rt 4.502 min; m/z 394 [M+H]+.

Provenance & Evidence