Water → 4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1,3-dimethyl-1H-pyrazole-5-carboxamide

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A mixture of 4-bromo-1,3-dimethyl-1H-pyrazole-5-carboxylic acid (20.0 mg, 0.0913 mmol), NH4Cl (48.8 mg, 0.913 mmol), TBTU (58.6 mg, 0.183 mmol), DIPEA (0.159 mL, 0.913 mmol) and DMF (2 mL, 20 mmol) was stirred at rt for 10 min. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3×) to remove carboxylic acid starting material. The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15.0 mg, 0.0348 mmol), (1,1′bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.34 mg, 0.00456 mmol), K2CO3 (18.9 mg, 0.137 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95° C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.3 Hz, 3H), 2.04 (s, 3H), 3.66 (br. s., 3H), 3.95 (s, 3H), 5.11 (q, J=6.8 Hz, 1H), 6.90 (dd, J=9.0, 4.2 Hz, 1H), 7.08 (t, J=8.8 Hz, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.45 (s, 1H), 8.07 (br. s., 1H). MS (ES+): m/z=442.14/444.14 (100/50) [MH+]. HPLC: tR=1.37 min (polar—3 min, UPLC-ACQUITY).

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