Dimethylformamide → N-(4,6-dichloropyridin-3-yl)-N2-(3-methylbutyl)alaninamide
Reaction equation
Br[CH:2]([CH3:14])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([Cl:13])=[CH:10][C:11]=1[Cl:12])=[O:4].[C:15](=O)([O-])[O-].[K+].[K+].ClC1N=[C:26](Cl)[C:25]([N+]([O-])=O)=[CH:24]N=1.C[N:33]([CH:35]=O)C>O>[Cl:12][C:11]1[CH:10]=[C:9]([Cl:13])[N:8]=[CH:7][C:6]=1[NH:5][C:3](=[O:4])[C@H:2]([CH3:14])[NH:33][CH2:35][CH2:24][CH:25]([CH3:26])[CH3:15]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
To a stirred solution of 2-bromo-N-(4,6-dichloropyridin-3-yl)propanamide (500 mg, 1.68 mmol) in DMF (4 mL) was added potassium carbonate (465 mg, 3.36 mmol) and isoamylamine (4, 0.512 mg, 5.88 mmol), the reaction mixture was then heated to 80° C. and stirred at the same temperature for 2 h. The reaction mixture was then cooled to rt, diluted with water (20 mL) and extracted with ethyl acetate (25 mL×3). The combined organic phases were washed with water, dried over Na2SO4 and evaporated to give a crude residue, which was purified by silica gel column chromatography (eluent: 25% ethyl acetate in hexane) to give desired product (Yield: 69%). 1HNMR (CDCl3, 300 MHz) δ 0.91-0.98 (m, 6H), 1.39-1.43 (m, 3H), 1.60-1.75 (m, 2H), 2.59-2.76 (m, 2H), 3.22-3.31 (m, 2H), 7.41 (s, 1H), 9.51 (s, 1H), 10.20 (br s, 1H).
Workup
- temperatureThe reaction mixture was then cooled to rt
- extractionextracted with ethyl acetate (25 mL×3)
- washThe combined organic phases were washed with water
- dry with materialdried over Na2SO4
- customevaporated
- customto give a crude residue, which
- customwas purified by silica gel column chromatography (eluent: 25% ethyl acetate in hexane)
Sources & evidence
- ORD record
- ord-e97dc0873913429eb2f9bceb94592e52
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09351974B2
Reaction notes
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