Tetrahydrofuran → cyclohexyl[1-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-4-yl]methanol
Reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:14]=[CH:15][C:8]=23)[CH:6]=1.C1COCC1.C([Li])CCC.CCCCCC.[CH:40]1([CH:46]=[O:47])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>>[CH:40]1([CH:46]([C:2]2[CH:3]=[N:4][N:5]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:14]=[CH:15][C:8]=34)[CH:6]=2)[OH:47])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1Participants
6
Reactant 5
Product 1
Conditions
- Temperature
- -78 °C
Procedure
A mixture of 4-(4-bromo-1H-pyrazol-1-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (50.0 mg, 0.000127 mol) in THF (2.0 mL, 0.025 mol) under a nitrogen atmosphere was cooled to −78° C. and 1.6 M n-butyllithium in hexane (0.10 mL, 0.00016 mol) was added slowly. The mixture was stirred for 15 min and then treated with cyclohexanecarboxaldehyde (25.0 μL, 0.000208 mol). After 20 min at −78° C., the reaction was partitioned between water and EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give the cyclohexyl[1-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-4-yl]methanol as a crude residue, LC/MS (M+H)+: 427.
Workup
- waitAfter 20 min at −78° C.
- customthe reaction was partitioned between water and EtOAc
- washThe combined organic layer was washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-05b94190b6c34afe84c254a8621843bc
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415362B2
Reaction notes
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