Acetonitrile → HCID 86690142, compound

Temperature

60 °C

Carbonyl diimidazole (1.266 g, 7.81 mmol) was added to a stirred solution of 6-amino-2,2,7-trifluoro-4-(prop-2-ynyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (the product of Step 1.6 above, 1.0 g, 3.90 mmol) and triethylamine (0.571 ml, 4.10 mmol) in anhydrous acetonitrile (20 ml) at room temperature under nitrogen. The resulting mixture was heated to 60° C., and then methyl 2-(methylamino)benzoate (0.602 ml, 4.10 mmol) was added. The reaction was heated to reflux for 1 h, after which time the LCMS analysis of a small sample that was subjected to quenching with benzylamine followed by aqueous acidic work up indicated that the reaction was complete. The reaction mixture was then poured into a stirred mixture of ethyl acetate (100 ml) and 1N aqueous hydrochloric acid (100 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate and evaporated in vacuo to yield 1.69 g of crude product. This was triturated overnight with dichloromethane, and the resulting precipitate was filtered off, washed with diisopropyl ether and dried over anhydrous sodium sulfate to give 860 mg of the title compound as an off-white powder.

1. temperatureThe reaction was heated
2. temperatureto reflux for 1 h
3. customto quenching with benzylamine
4. additionThe reaction mixture was then poured into a stirred mixture of ethyl acetate (100 ml) and 1N aqueous hydrochloric acid (100 ml)
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with ethyl acetate
7. washThe combined organic phases were washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. customevaporated in vacuo
10. customto yield 1.69 g of crude product
11. customThis was triturated overnight with dichloromethane
12. filtrationthe resulting precipitate was filtered off
13. washwashed with diisopropyl ether
14. dry with materialdried over anhydrous sodium sulfate

ORD record

ord-72f172cf4a324fb699e02644e69b4282

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669208B2