StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Ethylene Glycol → (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-carboxymethylsulfanyl-pyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

HRID 506351
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 506351
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22](I)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].C[O:44][C:45](=[O:48])[CH2:46][SH:47].C(O)CO.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.[Cu](I)I.O>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([S:47][CH2:46][C:45]([OH:48])=[O:44])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 174Ethylene GlycolHCID 11430Potassium CarbonateHCID 16907Methyl ThioglycolateHCID 86610559(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-iodopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Produkt 1

HCID 86610582
(2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-carboxymethylsulfanyl-pyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 962WaterLösungsmittelHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-iodopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (400 mg) is dissolved in isopropyl alcohol (2 ml), then thereto are added thioglycolic acid methyl ester (120 μl), copper iodide (20 mg), ethylene glycol (62 μl) and potassium carbonate (156 mg), and the mixture is stirred at 80° C. under nitrogen flow overnight. After allowing to cool to room temperature, water is added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer is washed with a saturated brine twice, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in methanol (6 ml), then thereto are added 1M-aqueous sodium hydroxide solution (3 ml) and tetrahydrofuran (6 ml), and the mixture is stirred at room temperature for 10 minutes. Ten % aqueous citric acid solution is added to the reaction mixture and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine twice, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=2:1→1:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-carboxymethylsulfanyl-pyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (153 mg).MS (m/z): 674 [M+H]+

Aufarbeitung

  1. temperatureto cool to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer is washed with a saturated brine twice
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting residue is dissolved in methanol (6 ml)
  7. additionare added 1M-aqueous sodium hydroxide solution (3 ml) and tetrahydrofuran (6 ml)
  8. stirringthe mixture is stirred at room temperature for 10 minutes
  9. additionTen % aqueous citric acid solution is added to the reaction mixture
  10. extractionthe mixture is extracted with ethyl acetate
  11. washThe organic layer is washed with a saturated brine twice
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=2:1→1:1)

Quellen und Nachweise

ORD-Eintrag
ord-1faa15c182224f4ab3b7b915e747523d
Quelldatensatz
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07781443B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion