反应详情

温度

85 °C

To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile (example 221) (215 mg, 0.48 mmole) in THF (3 mL) are added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid tert-butyl ester (191 mg, 0.63 mmole), 1M aqueous K2CO3 (2 mL) and PdCl2(dppf)2 (20 mg). The flask is evacuated and filled with argon. The reaction mixture is heated at 85° C. for 24 hours. AcOEt is added and the organic phase is washed with water, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) (100:0) to (95:5) to give 4-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester melting at 95° C.

1. customThe flask is evacuated
2. additionfilled with argon
3. additionAcOEt is added
4. washthe organic phase is washed with water
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customthe solvent removed under reduced pressure
8. customThe residue is purified by silica gel chromatography
9. washeluting with (CH2Cl2:MeOH) (100:0) to (95:5)