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

Temperature

25 °C

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.

1. customequipped with a reflux condenser
2. stirringThe reaction mixture was stirred in a 105° C. oil bath for 15 min
3. temperatureto cool to 25° C.
4. custompartitioned between EtOAc (150 mL) and 1% aq NaHSO3 (100 mL)
5. customthe organic phase was separated
6. concentrationconcentrated in vacuo to a brown solid (1.1 g)
7. additionThe solid was treated with phosphorous oxychloride (10 mL, Aldrich)
8. stirringstirred in a 100° C. oil bath for 1 h
9. temperatureAfter cooling to room temp
10. customthe reaction was quenched by slow addition to MeOH (200 mL)
11. concentrationconcentrated in vacuo
12. additionThe residue was treated with a mixture of 30% NH4OH and ice (200 mL)
13. extractionextracted with EtOAc (2×100 mL)
14. extractionThe combined organic extract
15. washwas washed with satd NaCl (50 mL)
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated in vacuo
19. customPurification by silica gel chromatography (30% EtOAc in hexane)
20. customprovided

ORD record

ord-23e0eee611f44faf95c792abc0f804c7

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07396831B2