Triethylamine → (E)-ethyl 3-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)acrylate

Temperature

110 °C

(a)(b) 1-(4-Fluorophenyl)-6-methyl-1H-indazol-5-ol [(484 mg, 2.0 mmol; prepared as described in Example 105(c)] was dissolved in DCM (20 mL) and pyridine was added (0.16 mL, 2 mmol) followed by triflic anhydride (0.36 mL, 2.1 mmol). After 1 h, the reaction was washed with 1 M HCl and the aqueous layer was dried over MgSO4, filtered, and concentrated. The crude 1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yltrifluoromethanesulfonate was taken up in 20 mL DMF, transferred to a stainless steel pressure bomb, and treated with ethyl acrylate (200 mg, 2 mmol), triethylamine (0.28 mL, 2 mmol), and Pd(PPh3)2Cl2 (160 mg, 0.2 mmol) and heated at 110° C. for 6 h. The reaction was incomplete so additional ethyl acrylate (200 mg, 2 mmol) and Pd(PPh3)2Cl2 (160 mg, 0.2 mmol) was added and the reaction was sealed and heated for 16 h. The reaction was cooled, diluted with EtOAc, washed with brine, and the organic phase was dried over MgSO4, filtered, and concentrated. The residue was purified by MPLC using SiO2 and a 1:9 EtOAc/hexane to 1:1 gradient. Obtained 350 mg (54% yield, 2 steps) of (E)-ethyl 3-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)acrylate. MS found: (M+H)+=325.

1. customprepared
2. washthe reaction was washed with 1 M HCl
3. dry with materialthe aqueous layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. additionwas added
7. customthe reaction was sealed
8. temperatureheated for 16 h
9. temperatureThe reaction was cooled
10. washwashed with brine
11. dry with materialthe organic phase was dried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was purified by MPLC

ORD record

ord-830026aadcbc449cb4ac117c1208f06f

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08067447B2