Hydrochloric Acid → HCID 131727490, compound

Participants

Reaction Conditions

Reaction Steps

4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine (70 mg, 0.29 mmol, Compound C of Example 1) and 2-chloro-N-methylnicotinamide (59 mg, 0.29 mmol) were suspended in 3:1 isopropanol-NMP (2.9 mL). 4N HCl in 1,4-dioxane (0.22 mL, 0.86 mmol) was added and the reaction was heated to 100° C. for 168 h. The reaction was diluted with 30 mL of H2O and then basified with sat. aq. NaHCO3 soln. (5 mL). The aqueous layer was extracted EtOAc (3×10 mL). The combined organic layers were washed with 10% LiCl (15 mL), dried (MgSO4) and concentrated. The crude product was purified by preparative (RP) HPLC chromatography (YMC S5 ODS, 30×75 mm, 10 minute gradient from 33% to 90% aqueous methanol with 0.1% TFA, 40 mL/min). The fractions containing the desired product were combined and concentrated. The product residue was dissolved in MeOH (2 mL) and acidified with 4N HCl in 1,4-dioxane (0.10 mL). Concentration afford the desired product as a brown solid (3.3 mg, >99% HPLC purity). 1H NMR (CD3OD) δ 8.33 (d, 1H, J=2.54 Hz), 8.31 (d, 1H, J=7.12 Hz), 8.17 (dd, 1H, J=13.48, 2.29 Hz), 8.09 (d, 1H, J=2.03 Hz), 7.56 (d, 1H, J=3.56 Hz), 7.33-7.43 (m, 2H), 6.91 (d, 1H, J=6.61 Hz), 6.68 (d, 1H, J=3.56 Hz), 2.93 (s, 3H); MS(ESI+) m/z 412.2 (M+H)+.

Provenance & Evidence