p-Toluenesulfonic acid → HCID 71451847, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-5-methoxyphenyl)-(morpholino)methanone (120 mg, 0.28 mmol) in dioxane (2 mL) was added pTSA (52 mg, 0.28 mmol) and D4-cyclopropylamine (17 mg, 0.28 mmol). The mixture was heated to 100° C. for 2 hours. LSMS of crude sample indicated only 10% of desired material. DIPEA (100 μL, 0.56 mmol) and D4-cyclopropylamine (17 mg, 0.28 mmol) were added and the mixture was heated to 100° C. for one hour. After return to room temperature, DCM (20 mL) and saturated aqueous sodium bicarbonate solution (15 mL) were added. The separated organic phase was passed through a hydrophobic frit and the solvent was removed in vacuo. The residue was purified by reversed phase HPLC to give (4-(4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-5-methoxyphenyl)(morpholino)-methanone (42 mg, 33%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=460 at 3.41 min. 1H NMR (400 MHz, CDCl3): δ 8.77 (d, J=12.8 Hz, 1H), 8.20 (s, 1H), 7.94 (s, 1H), 6.91 (d, J=5.6 Hz, 1H), 5.48 (s, 1H), 3.92 (s, 3H), 3.80-3.74 (m, 4H), 3.69-3.67 (m, 2H), 3.44-3.43 (m, 2H).

Provenance & Evidence