Reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=1)([CH3:4])([CH3:3])[CH3:2].CNCCN(C)C.C([Li])CCC.[I:28]I>C1COCC1>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH3:14])[C:13]=1[I:28])([CH3:4])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- -78 °C
Procedure
(5-Methyl-pyridin-3-yl)-carbamic acid tert-butyl ester (255 mg, 1.2 mmol, Example 139: step a) and trimethylethylenediamine (905 μL, 6.0 mmol) were dissolved into THF (4 mL) and cooled to −78° C. To this was added n-Butyllithium (2.5M, 2.4 mL, 6.0 mmol). The reaction was stirred at −78° C. for 30 minutes and then warmed to RT for 30 minutes. Iodine (1.5 g, 6.0 mmol) was dissolved into THF (4 mL) and added to the reaction mixture at −78° C. slowly. The reaction was warmed to RT for 1 hour and the solvents were removed in vacuo. The residue was dissolved into EtOAc and washed with brine and water. The combined organic layers were dried (MgSO4) and solvents were removed in vacuo followed by purification by flash column chromatography (SiO2) (50% EtOAc in hexanes) that yielded the title compound as a yellow solid (55 mg, 14%). 1H-NMR (CDCl3): δ 8.91 (s, 1H), 8.07 (s, 1H), 6.81 (br s, 1H), 2.44 (s, 3H), 1.56 (s, 9H). ESI-MS (m/z): Calcd. for C11H15IN2O2: 335.0 (M+1); found: 334.9.
Workup
- temperaturewarmed to RT for 30 minutes
- additionadded to the reaction mixture at −78° C. slowly
- temperatureThe reaction was warmed to RT for 1 hour
- customthe solvents were removed in vacuo
- dissolutionThe residue was dissolved into EtOAc
- washwashed with brine and water
- dry with materialThe combined organic layers were dried (MgSO4) and solvents
- customwere removed in vacuo
- customfollowed by purification by flash column chromatography (SiO2) (50% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-a9fb5039e9944f5ea5e3f040f9088009
- Source dataset
- uspto-grants-2006_09
- Patent number
- US07109354B2
Linked notes
Loading…