p-Toluenesulfonic acid → (4-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-5-methoxy-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), 2,5-dichloro-N-methylpyrimidin-4-amine (55 mg, 0.31 mmol) and para-toluene sulfonic acid (59 mg, 0.31 mmol) in dioxane (4 mL) was heated to 100° C. for 36 h. Saturated aqueous sodium bicarbonate solution (10 mL) and DCM (10 mL) were added and the organic phase was passed through a hydrophobic frit and the solvent was removed in vacuo. Purification of the residue via silica gel column chromatography (0-10% EtOAc in iso-hexane) gave (4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)-5-methoxy-2-(trifluoromethyl)phenyl)(morpholino)methanone (11 mg, 8%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=446 at 3.60 min. 1H NMR (400 MHz, CDCl3): δ 8.97 (s, 1H), 8.40 (br s, 1H), 7.90 (s, 1H), 6.76 (s, 1H), 5.59 (q, J=4.9 Hz, 1H), 3.96 (s, 3H), 3.95-3.87 (m, 1H), 3.82-3.69 (m, 3H), 3.62-3.56 (m, 2H), 3.26-3.20 (m, 2H), 3.13 (d, J=4.9 Hz, 3H).

Provenance & Evidence