Dimethylformamide → 3-hydroxy-1-methyl-2-{2,2,2-trifluoro-1-[methyl(prop-2-yn-1-yl)amino]ethyl}pyridin-4(1H)-one

HRID 1519040Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1519040
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]

Komponenten

7

Edukt 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 96160N-methylpropyn-2-ylamineHCID 67282261HCID 67282261, Verbindung

Produkt 1

HCID 866728123-hydroxy-1-methyl-2-{2,2,2-trifluoro-1-[methyl(prop-2-yn-1-yl)amino]ethyl}pyridin-4(1H)-oneAusbeute 46,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at RT for overnight
  2. filtrationThe solid was filtered off
  3. concentrationthe filtrate was concentrated to dryness
  4. customThe residue was purified by flash chromatography on silica gel (5% MeOH in CH2Cl2 as eluant)

Quellen und Nachweise

ORD-Eintrag
ord-74549448097648eba36a76674f383928
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073865B2

Notizen zur Reaktion

Wird geladen…