p-Toluenesulfonic acid → (5-Methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-(trifluoromethyl)phenyl)(morpholino)methanone

Participants

Reaction Conditions

Reaction Steps

A mixture of (4-amino-5-methoxy-2-(trifluoromethyl)phenyl)(morpholino)methanone (94 mg, 0.31 mmol), 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (66 mg, 0.31 mmol) and para-toluene sulfonic acid (59 mg, 0.31 mmol) in dioxane (4 mL) was heated to 100° C. for 2 h. Saturated aqueous sodium bicarbonate solution (10 mL) and DCM (10 mL) were added and the organic phase was passed through a hydrophobic frit. The solvent was removed in vacuo and the residue was purified by reversed phase HPLC to give (5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-(trifluoromethyl)phenyl)(morpholino)methanone (111 mg, 75%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=480 at 3.32 min. 1H NMR (400 MHz, CDCl3): δ 9.13 (s, 1H), 8.19 (s, 1H), 7.82 (s, 1H), 6.77 (s, 1H), 5.34 (q, J=4.7 Hz, 1H), 3.97 (s, 3H), 3.95-3.88 (m, 1H), 3.83-3.68 (m, 3H), 3.65-3.55 (m, 2H), 3.27-3.21 (m, 2H), 3.13 (d, J=4.7 Hz, 3H).

Provenance & Evidence