Hydrochloric Acid → HCID 56659710, compound

Participants

Reaction Conditions

Reaction Steps

N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-acetamide (170.0 mg, 0.5607 mmol) was added into a Vial, followed by a solution of 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (103.0 mg, 0.5413 mmol) in 2-Methoxyethanol (7 mL, 90 mmol). 4 M of Hydrogen chloride in 1,4-Dioxane (0.20 mL) was added and the reaction was heated at 120° C. After 4.5 h, the reaction was cooled to room temperature, Macroporous carbonate resin (3.16 mmol/g loading; 530 mg, 1.68 mmol) was added and stirred 30 min. The polymer was filtered off, and the solvent removed in vacuo. The residue was dissolved in DCM, concentrated onto Celite, then chromatographed (2×12 g SiO2, ISCO, 0-10% (5% NH4OH:MeOH):DCM) to afford N-{(1R,2R)-2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-acetamide as a beige solid (170 mg, 69%). m.p.=248-250° C.; LCMS (m/e) 457 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.88 (s, 1H), 7.28 (m, 2H), 7.04 (d, 1H, J=7.5 Hz), 6.77 (s, 1H), 6.02 (s, 1H), 5.73 (s, 1H), 3.81 (m, 2H), 2.81-2.91 (m, 4H), 2.5-2.6 (m, 6H), 2.26 (m, 1H), 2.13 (m, 1H), 1.81 (m, 2H), 1.71 (s, 3H), 1.2-1.4 (m, 4H), 1.10 (t, 3H, J=7 Hz).

Provenance & Evidence