Hydrochloric Acid → HCID 131729554, compound

Participants

Reaction Conditions

Reaction Steps

(2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (104 mg, 0.293 mmol) was added into a vial, followed by a solution of 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (55.0 mg, 0.289 mmol) in 2-Methoxyethanol (3 mL). 4 M of Hydrogen chloride in 1,4-Dioxane (0.10 mL) was added and the reaction was heated at 120° C. After 6 h, Macroporous carbonate resin (3.16 mmol/g loading; 150 mg, 0.474 mmol) was added and the reaction was cooled to room temperature, stirred overnight, then was concentrated in vacuo onto Celite, and chromatographed (2×24 g ISCO Amine column, 0-0.5% MeOH:DCM). Product is ca. 75% pure; rechromatograph, (2×4 g ISCO Amine column, DCM) to isolate 5-Chloro-N*2*-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine as a beige powder (25 mg, 17%). m.p.=157-162° C.; LCMS (m/e) 509 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.25 (d, 1H, J=8.8 Hz), 8.00 (s, 1H), 7.58 (s, 1H), 7.42 (s, 1H), 7.18 (m, 1H), 7.02 (m, 1H), 6.83 (s, 1H), 6.54 (s, 1H), 6.49 (d, 1H, J=9.1 Hz), 3.92 (s, 3H), 3.89 (t, 4H, J=4.8 Hz), 3.15 (t, 4H, J=4.8 Hz), 2.91 (m, 4H), 2.64 (m, 4H), 2.57 (q, 2H, J=7 Hz), 1.10 (t, 1H, J=7 Hz).

Provenance & Evidence