反应详情

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-cyano-5-fluoro-indol-1-yl)-amide (120 mg, 0.31 mmol), TMSN3 (62 μL, 0.465 mmol), and TBAF (0.155 μL, 0.155 mmol, 1 M in THF) in toluene (3 mL) is heated at 80° C. for 18 h. The mixture is cooled, diluted with EtOAc, and washed with 1 M HCl. The organic layer is extracted with Na2CO3. The aqueous layer is acidified to pH ˜3 with 3 N aqueous HCl, extracted with EtOAc The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(1H-tetrazol-5-yl)-indol-1-yl]-amide (100 mg, 75%). MS: 433 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.81 (s, 3H), 7.28 (m, 1H), 7.47 (m, 1H), 7.67 (m, 1H), 7.73 (m, 1H), 8.01 (m, 1H), 8.21 (m, 1H), 8.33 (m, 1H), 8.36 (s, 1H), 9.33 (s, 1H). IC50=5 nM.

1. temperatureThe mixture is cooled
2. washwashed with 1 M HCl
3. extractionThe organic layer is extracted with Na2CO3
4. extractionextracted with EtOAc The organic layer
5. customis separated
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo