Trifluoroacetic acid → HCID 66858461, compound

Temperature

0 °C

A 25 mL round bottom flask was charged with copper (I) iodide (8.16 mg, 0.043 mmol) in THF (1 mL), and cooled to 0° C. A solution of methylmagnesium bromide (1.53 mL, 2.142 mmol, 1.4 M in THF) was added dropwise to the stirred solution and stirred for 20 min. To solution of methyl cuprate was added 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (100 mg, 0.214 mmol, from example 137) in THF (1 mL) and the reaction was stirred at 0° C. for an additional 2 h. The resulting mixture was quenched slowly with saturated ammonium chloride, and the aqueous layer was washed with EtOAc (×3). The combined organic layers were then washed with brine (100 mL), dried over sodium sulfate and concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the titled compound (21.6 mg, 17% yield) as a TFA salt. LC-MS (M+H)+ 483.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 10.36 (1 H, br. s.), 9.30 (1 H, br. s.), 8.05 (1 H, s), 7.22-7.33 (2 H, m), 7.08-7.20 (6 H, m), 4.62-4.76 (2 H, m), 4.34-4.46 (1 H, m), 3.82-3.92 (3 H, m), 2.16-2.34 (2 H, m), 2.04-2.14 (1 H, m), 1.92-2.04 (1 H, m), 1.43-1.53 (3 H, m).

1. stirringthe reaction was stirred at 0° C. for an additional 2 h
2. customThe resulting mixture was quenched slowly with saturated ammonium chloride
3. washthe aqueous layer was washed with EtOAc (×3)
4. washThe combined organic layers were then washed with brine (100 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe crude product was purified

ORD record

ord-e819584803b94f1cb8c003b98aea419c

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349880B2