Hydrochloric Acid → 2-{2-[3-bromo-10-(2,2,2-trifluoro-acetyl)-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino]-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide

Participants

Reaction Conditions

Reaction Steps

1-(4-Amino-3-bromo-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-10-yl)-2,2,2-trifluoro-ethanone (76 mg, 0.209 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (68.4 mg, 0.230 mmol, 1.1 eq) were dissolved in IPA (2 mL). 4.0 M HCl in dioxane (57.5 μL, 0.230 mmol, 1.1 eq) was added and the reaction was heated at 120° C. in a microwave for 4 hours. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by silica gel chromatography using a gradient of 0-50% EtOAc/hex as the eluting solvent to obtain 2-{2-[3-bromo-10-(2,2,2-trifluoro-acetyl)-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino]-5-chloro-pyrimidin-4-ylamino}-N-methyl-benzamide as a pale yellow foam (24.99 mg, 19%). LCMS (m/e) 623 (M+1); 1H-NMR (CDCl3, 400 MHz) major rotomer δ 11.03 (s, 1H), 8.55 (d, 1H, J=8.4 Hz), 8.26 (s, 1H), 8.14 (s, 1H), 7.55-7.26 (m, 4H), 7.15-7.05 (m, 1H), 6.30-6.20 (m, 1H), 4.23 (dd, 1H, J=5.3 and 13.5 Hz), 3.95-3.83 (m, 1H), 3.47-3.38 (m, 1H), 3.30-3.20 (m, 1H), 3.20-3.09 (m, 1H), 3.04 (s, 3H), 3.06-2.97 (m, 1H), 2.10-1.97 (m, 2H), 1.87-1.70 (m, 2H).

Provenance & Evidence