Diisopropylethylamine → Ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate
Reaction equation
[CH3:1][C:2]1([CH3:8])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[Br:18][C:19]1[C:20](Cl)=[C:21]([C:27](=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:22]([CH3:26])=[N:23][C:24]=1[CH3:25]>CC#N>[Br:18][C:19]1[C:20]([N:5]2[CH2:6][CH2:7][C:2]([CH3:8])([CH3:1])[CH2:3][CH2:4]2)=[C:21]([C:27](=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:22]([CH3:26])=[N:23][C:24]=1[CH3:25]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 4,4-dimethylpiperidine (1.245 g, 11.00 mmol) and DIEA (3.49 ml, 20.00 mmol) in anhydrous CH3CN (40 mL) was added ethyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (3.21 g, 10 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80° C.). After 22 h, the reaction mixture was concentrated and the residue was purified by flash chromatography using 1-lit each 2.5, 5, 7.5 and 10% EtOAc/Hex to afford ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate (2.846 g, 7.16 mmol, 71.6% yield) as yellow solid. 1H NMR (500 MHz, CDCl3) δ 4.37 (q, J=7.1 Hz, 2H), 3.67-2.75 (br.s., 4H), 2.71 (s, 3H), 2.44 (s, 3H), 1.42 (t, J=7.1 Hz, 3H), 1.38 (t, J=5.6 Hz, 4H), 1.00 (s, 6H). LCMS (M+H)=399.4.
Workup
- customThe resulting mixture was placed in a pre-heated oil bath
- custom(80° C.)
- concentrationthe reaction mixture was concentrated
- customthe residue was purified by flash chromatography
Sources & evidence
- ORD record
- ord-ccda779be53d40069e7b15f35a6f6161
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09193720B2
Reaction notes
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