Diethyl chlorophosphate → 5-cyano-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo [2,3-b]pyridin-3-yl)pyrimidin-2-yl diethyl phosphate

HRID 40845

Reaktionsgleichung

Reaktionsgleichung von HRID 40845
[OH:1][C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:17]([F:20])([F:19])[F:18])[CH:15]=3)[N:10]([S:21]([C:24]3[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:9]=2)[C:5]([C:31]#[N:32])=[CH:4][N:3]=1.CC(C)([O-])C.[K+].[CH2:39]([O:41][P:42](Cl)([O:44][CH2:45][CH3:46])=[O:43])[CH3:40].C([O-])(O)=O.[Na+]>C1COCC1>[P:42]([O:44][CH2:45][CH3:46])([O:41][CH2:39][CH3:40])([O:1][C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([C:17]([F:18])([F:20])[F:19])[CH:15]=3)[N:10]([S:21]([C:24]3[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:9]=2)[C:5]([C:31]#[N:32])=[CH:4][N:3]=1)=[O:43]

Komponenten

6

Edukt 4

HCID 13139Diethyl chlorophosphateHCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 178427354HCID 178427354, Verbindung

Produkt 1

HCID 594143445-cyano-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo [2,3-b]pyridin-3-yl)pyrimidin-2-yl diethyl phosphateAusbeute 58,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

2-hydroxy-4-(1-tosyl-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-5-carbonitrile (87% pure, 1.23 g, 2.329 mmol) in dry THF (24.60 mL) was stirred at −25° C. and treated with potassium t-butoxide (2.795 mL of 1.0 M, 2.795 mmol) in THF. The reaction mixture was warmed up to 0° C. for 20 minutes, cooled to −50° C. and treated with diethylchlorophosphate (482.3 mg, 403.9 μL, 2.795 mmol). The reaction mixture was stirred at −40° C. for 20 minutes and at room temperature for 2 hours. The reaction mixture was diluted with ice cold ethyl acetate (60 mL), cooled in ice and shaken quickly with ice cold water containing 1M HCl (2.8 mL, 2.8 mmol), basified with aqueous NaHCO3 and extracted into ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated to give a pale yellow solid which was triturated with ether and filtered to give a pale yellow solid (810 mg). The mother liquors were concentrated in vacuo and the residue purified on silica gel by flash column chromatography to afford a colourless solid (219 mg) (total: 1.029 g, 74% yield).

Aufarbeitung

  1. temperaturecooled to −50° C.
  2. temperaturecooled in ice
  3. extractionextracted into ethyl acetate
  4. dry with materialThe organic extracts were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give a pale yellow solid which
  7. customwas triturated with ether
  8. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-814f531bbd464f5c8a7e1f6f6a067205
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530489B2

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