Dimethylformamide → 3-hydroxy-1-methyl-2-{2,2,2-trifluoro-1-[methyl(prop-2-yn-1-yl)amino]ethyl}pyridin-4(1H)-one
Reaction equation
CN(C=O)C.C(Cl)(=O)C(Cl)=O.[OH:12][C:13]1[C:18](=[O:19])[CH:17]=[CH:16][N:15]([CH3:20])[C:14]=1[CH:21](O)[C:22]([F:25])([F:24])[F:23].CCN(CC)CC.[CH3:34][NH:35][CH2:36][C:37]#[CH:38]>C(#N)C>[OH:12][C:13]1[C:18](=[O:19])[CH:17]=[CH:16][N:15]([CH3:20])[C:14]=1[CH:21]([N:35]([CH3:34])[CH2:36][C:37]#[CH:38])[C:22]([F:25])([F:24])[F:23]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To 20 mL acetonitrile cooled in an ice-water bath was added DMF (0.42 mL, 5.4 mmol) followed by oxalyl chloride (0.47 mL, 5.4 mmol) dropwise. To this resulting suspension was added 3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one (1.0 g, 4.5 mmol) in one portion. The mixture was then stirred for 2 h. Then, Et3N (2.50 mL, 17.9 mmol) was added to this reaction mixture followed by N-methyl propargylamine (0.75 mL, 9.0 mmol). The reaction mixture was stirred at RT for overnight. The solid was filtered off, and the filtrate was concentrated to dryness. The residue was purified by flash chromatography on silica gel (5% MeOH in CH2Cl2 as eluant) to afford the title compound, Apo7057 (570 mg) as an orange powder. Yield=46.4%; 1H NMR (400 MHz, DMSO+a few drops of D2O) δ (ppm): 7.6 (br. s., 1H), 6.25 (d, J=7.1 Hz, 1H), 5.15 (br. s., 1H), 3.87 (s, 3H), 3.37-3.67 (m, 2H), 3.23 (br. s., 1H), 2.32 (br. s., 3H); MS m/z 275 [M+1]+, 206 (100%).
Workup
- stirringThe reaction mixture was stirred at RT for overnight
- filtrationThe solid was filtered off
- concentrationthe filtrate was concentrated to dryness
- customThe residue was purified by flash chromatography on silica gel (5% MeOH in CH2Cl2 as eluant)
Sources & evidence
- ORD record
- ord-74549448097648eba36a76674f383928
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073865B2
Reaction notes
Loading…