Triethylamine → 2-[1-(dimethylamino)-2,2,2-trifluoroethyl]-3-hydroxy-1-methylpyridin-4(1H)-one
Reaction equation
[OH:1][C:2]1[C:7](=[O:8])[CH:6]=[CH:5][N:4]([CH3:9])[C:3]=1[CH:10](O)[C:11]([F:14])([F:13])[F:12].Cl.[CH3:17][NH:18][CH3:19].CCN(CC)CC>C(#N)C>[CH3:17][N:18]([CH3:19])[CH:10]([C:3]1[N:4]([CH3:9])[CH:5]=[CH:6][C:7](=[O:8])[C:2]=1[OH:1])[C:11]([F:14])([F:13])[F:12]Participants
Procedure
To a suspension of 3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one (5.00 g, 22.4 mmol) in 40 mL of acetonitrile at ice-water bath was added Vilsmeier's reagent (4.30 g, 33.6 mmol) portionwise. The resulting mixture was stirred for 2 h before being added to a suspension of dimethylamine hydrochloride (6.00 g, 73.6 mmol) and Et3N (15.0 mL, 107.6 mmol) in 30 mL of acetonitrile. The resulting suspension 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 (10% MeOH in EtOAc as eluant) to afford title compound, Apo7041 (1.8 g). Yield=32%; 1H NMR (90 MHz, CD3OD-D4) δ (ppm): 7.63 (d, J=7.3 Hz, 1H), 6.41 (d, J=7.3 Hz, 1H), 4.78 (q, J=8.1 Hz, 1H), 3.99 (s, 3H), 2.41 (s, 6H); MS m/z 273 [M+Na]+, 251 [M+1]+, 206 (100%).
Workup
- stirringThe resulting suspension 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 (10% MeOH in EtOAc as eluant)
Sources & evidence
- ORD record
- ord-e8d84901ba164be8b936534c4b7d57fe
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09073865B2
Reaction notes
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