Methanesulfonamide → 2-(4-{5-fluoro-4-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}-1H-pyrazol-1-yl)-N-(methylsulfonyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-(5-fluoro-4-(2-(1-hydroxycyclobutyl)thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid (Example 65B) (75 mg, 0.181 mmol) in N,N-dimethylformamide (1.0 mL) was added methanesulfonamide (20.7 mg, 0.218 mmol), 4-dimethylaminopyridine (66.5 mg, 0.544 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (52.2 mg, 0.272 mmol). The solution was heated to 45° C. for 4 hours. The reaction was cooled to room temperature and diluted with dimethyl sulfoxide (1 mL). The resulting solution was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD 5 um column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid) to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.35 (s, 1H), 12.30-12.18 (m, 1H), 8.43 (s, 1H), 8.35 (s, 1H), 8.22 (d, J=3.6 Hz, 1H), 8.16 (s, 1H), 7.07 (d, J=2.0 Hz, 1H), 6.67 (s, 1H), 5.10 (s, 2H), 3.29 (s, 3H), 2.64-2.56 (m, 2H), 2.46-2.32 (m, 2H), 2.05-1.87 (m, 2H); MS ESI(+) m/z 490.9 [M+H]+.

Provenance & Evidence