2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → HCID 10023954, compound

Participants

Reaction Conditions

Reaction Steps

7-[6-(4-(Trifluoromethylphenyl)pyrimidin-4-ylamino]-3,4-dihydro-1H-quinolin-2-one hydrochloride, Example 9(c), (500 mg, 1.2 mmol) was suspended in anhydrous 1,4-dioxane (10 mL), under N2, in a flame-dried, round-bottomed flask equipped with a reflux condenser. The suspension was magnetically stirred at 25° C. and treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (350 mg, 1.5 mmol, Aldrich) followed by bis(trimethylsilyl)trifluoroacetamide (1.4 mL, 5.3 mmol, Aldrich). The reaction mixture was stirred in a 105° C. oil bath for 15 min, then allowed to cool to 25° C. and partitioned between EtOAc (150 mL) and 1% aq NaHSO3 (100 mL). The resulting emulsion was allowed to settle, and the organic phase was separated and concentrated in vacuo to a brown solid (1.1 g). The solid was treated with phosphorous oxychloride (10 mL, Aldrich) and stirred in a 100° C. oil bath for 1 h. After cooling to room temp, the reaction was quenched by slow addition to MeOH (200 mL), then concentrated in vacuo. The residue was treated with a mixture of 30% NH4OH and ice (200 mL), then extracted with EtOAc (2×100 mL). The combined organic extract was washed with satd NaCl (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (30% EtOAc in hexane) provided a mixture of the title product and (2-methoxyquinolin-7-yl)-[6-(4-trifluoromethylphenyl)pyrimidin-4-yl]amine (Example 12), and the pure title product as a white solid. MS (ESI, pos. ion) m/z: 401 (M+1). MP: 233° C.

Provenance & Evidence