Pyridine → HCID 86274674, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2,2,2-trimethylacetamide (0.248 g, 2.453 mmol) in DCE (5 mL) was treated with oxalyl chloride (0.197 mL, 2.331 mmol), heated at 100° C. for 1 h, cooled to RT, added drop-wise to a solution of (R)—N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-3-(dimethylamino)pyrrolidine-1-carboxamide (0.600 g, 1.752 mmol) and pyridine (0.198 mL, 2.453 mmol) in THF (10 mL) and stirred at RT overnight. The mixture was concentrated to dryness, treated with satd. NH4Cl, extracted with EtOAc (4×) and the combined organics were washed with water, dried over Na2SO4 and concentrated to dryness. The residue was suspended in MeCN, sonicated and the resulting solid collected via filtration to afford (R)-3-(dimethylamino)-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-1-carboxamide (280 mg, 34%). 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (br s, 1H), 8.78 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.11 (d, J=5.7 Hz, 1H), 8.08 (d, J=8.9 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 6.61 (dd, J=5.7, 2.4 Hz, 1H), 3.62 (m, 1H), 3.52 (m, 1H), 3.27 (m, 1H), 3.08 (m, 1H), 2.65 (m, 1H), 2.15 (s, 6H), 2.08-1.95 (m, 1H), 1.65 (m, 1H), 1.21 (s, 9H); MS (ESI) m/z: 470.3 (M+H+).

Provenance & Evidence