Triethylamine → HCID 178423292, compound

Participants

Reaction Steps

To a −78° C. solution of 2-fluoro-1-methoxy-4-[2-methyl-4-piperidylpyrrolo[4,5-d]pyrimidin-6-yl]benzene (Example 119) (0.80 g, 2.35 mmol) in CH2Cl2 (40 mL) under a N2 atmosphere was added 1 M BBr3 (4.7 mL, 4.70 mmol). The reaction mixture was allowed to warm to room temperature. The mixture was stirred at room temperature for an additional 20 h. The reaction mixture was then poured onto ice-water (200 mL) and the pH of the aqueous solution was adjusted to pH 9 with the addition of NEt3 (4 mL). The resulting mixture was stirred at room temperature for 2 h. The solid which formed was removed by filtration and dicarded. The remaining solution was transferred to a separatory funnel. The organic solution was separated, washed with H2O (100 mL), saturated NaCl (100 mL), dried (MgSO4), filtered and concentrated under reduced pressure to afford 483 mg (62%) of 2-fluoro-4-(2-methyl-4-pyridylpyrrolo[4,5-d]pyrimidin-6-yl)phenol as a pale yellow colored solid. This compound (481 mg, 1.50 mmol) was dissolved in 4:2:1 EtOAc/MeOH/CH2Cl2 (50 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.50 mL, 1.50 mmol). The solution was allowed to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 315 mg (37%) of the title compound as a pale yellow colored solid. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.63 (br s, 6), 2.49 (s, 3), 3.96 (br s, 4), 6.76 (s, 1), 7.06 (dt, 1, J=1.9, 8.7), 7.58 (d, 1, J=8.5), 7.83 (dd, 1, J=1.9, 12.5), 10.47 (s, 1), 11.79 (s, 1), 14.12 (s, 1). MS m/z: 327 (M+1 for free base). Anal. Calcd for C18H19FN4O.HCl.1.5H2O: C, 55.45; H, 5.95; N, 14.37; Cl, 9.09. Found: C, 55.49; H, 5.87; N, 14.07; Cl, 9.03.

Provenance & Evidence