Hydrochloric Acid → HCID 86654068, compound

Participants

Reaction Steps

A solution of diethyl [3-methoxy-4-({4-[(2-methyl-5-oxido-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (Example 310, 35.0 mg, 0.0587 mmol) in EtOH (2.0 mL) was charged with iron (6.9 mg, 0.12 mmol) and heated to reflux. The reaction mixture was charged with 1 M of HCl in H2O (0.07 mL, 0.07 mmol) and stirred at reflux for 10 minutes. Additional 1 M of HCl in H2O (0.03 mL, 0.03 mmol) was added to the reaction mixture and stirred at reflux for 10 minutes. The reaction mixture was filtered through a pad of celite. The filtrate was quenched with NaHCO3 (10 mL) and extracted with EtOAc (15 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to a yellow solid. The crude material was purified by silica gel chromatography on an ISCO Combi-flash Rf system using DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a white solid (17.0 mg, 50%). The material was re-purified by HPLC. The fractions containing product were combined and concentrated to yield a white solid (4.3 mg, 13%). 1H NMR (DMSO-d6, 400 MHz): δ=8.71 (br. s., 1H), 8.60 (d, J=5.05 Hz, 1H), 8.54 (s, 1H), 8.47 (br. s., 1H), 8.32 (s, 1H), 7.41 (d, J=5.05 Hz, 1H), 6.95 (s, 1H), 6.85-6.92 (m, 1H), 4.57 (s, 2H), 3.90-4.01 (m, 4H), 3.84 (s, 3H), 3.21 (s, 1H), 3.06 (s, 3H), 1.19 (t, J=6.95 Hz, 6H). MS (ES+): m/z 581.10 [MH+] (TOF, polar).

Provenance & Evidence