Reaction Steps
N-{(1R,2R)-2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-2,2,2-trifluoro-acetamide (78 mg, 0.15 mmol) and Potassium carbonate (125 mg, 0.904 mmol) were combined in Methanol (10 mL), and were then heated at 45° C. After stirring 3.5 d, the reaction had reached ˜60% completion. After an additional 3 d, the mixture had evaporated to dryness, but the reaction had gone to completion as determined by HPLC of resolubilized material (DCM:MeOH). The mixture was reconcentrated to dryness after filtering off the solids. 1,4-Dioxane (5 mL) was added followed by Triethylamine (0.2 mL, 1.4 mmol) and N,N-Dimethylcarbamoyl chloride (21 uL, 0.23 mmol), and the reaction was stirred under an atmosphere of Nitrogen. After O.N. stirring, 0.5 mL DMF was added, and the mixture was sonicated to aid in solubilizing all the contents. After an additional 24 h, N,N-Dimethylcarbamoyl chloride (50 uL, 0.5 mmol) was added and stirring was continued. After 24 h, N,N-Dimethylcarbamoyl chloride (50 uL, 0.5 mmol) was added along with 3 mL dichloromethane to aid in solubility and to rinse the sidewalls of the flask. After 5 h, the contents were concentrated onto Celite and chromatographed on an ISCO column, eluting with 10% (5% NH4OH:MeOH):DCM. The product elutes at 10% polar solvent mix, and was collected and concentrated to afford 3-{(1R,2R)-2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-1,1-dimethyl-urea (52 mg, 70%) as a yellow film. LCMS (m/e) 486 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.85 (s, 1H), 7.28 (m, 2H), 7.03 (m, 2H), 6.08 (d, 1H, J=7.1 Hz), 4.85 (d, 1H, J=7.2 Hz), 3.82 (m, 1H), 3.71 (m, 1H), 2.94 (m, 5H), 2.68 (s, 6H), 2.62 (m, 7H), 2.28 (m, 1H), 2.15 (m, 1H), 1.80 (m, 2H), 1.2-1.4 (m, 5H), 1.12 (t, 3H, J=7.1 Hz).
