Cesium carbonate → 5-Bromo-1-(2,2-dimethoxyethyl)-1H-indazole
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[CH3:11][O:12][CH:13]([O:16][CH3:17])[CH2:14]Br.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:14][CH:13]([O:16][CH3:17])[O:12][CH3:11])[N:6]=[CH:5]2Participants
Conditions
- Temperature
- 40 °C
Procedure
To a solution of 5-bromo-1H-indazole (10.0 g, 51.2 mmol) in DMSO (120 mL) was added 2-bromoacetaldehyde dimethyl acetal (12.1 mL, 103 mmol) and Cs2CO3 (66.8 g, 205 mmol). The reaction mixture was stirred at 40° C. for 18 h; then the reaction mixture was diluted with H2O (100 mL) and EtOAc (175 mL). The aqueous layer was extracted with EtOAc (4×175 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated. Purification by flash chromatography (ISCO 330 g column, 95:5 hexanes/EtOAc to hexanes/EtOAc 50:50, 60 min, 40 mL/min) gave the title compound (8.52 g, 46%) as a light orange solid: 1H NMR (300 MHz, CDCl3) 7.94 (s, 1H), 7.85 (d, J=1.2, 1H), 7.48-7.42 (dd, J=8.9, 1.7 Hz, 1H), 7.37 (d, J=8.9 Hz, 1H), 4.71 (t, J=5.4 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.33 (s, 6H).
Workup
- extractionThe aqueous layer was extracted with EtOAc (4×175 mL)
- washThe combined organics were washed with brine (2×100 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
- customPurification by flash chromatography (ISCO 330 g column, 95:5 hexanes/EtOAc to hexanes/EtOAc 50:50, 60 min, 40 mL/min)
Sources & evidence
- ORD record
- ord-ecf3cb83eaf649a4b3e0a804b9ebbe25
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08268868B2
Reaction notes
Loading…