Potassium tert-butoxide → 2-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-8-oxa-2-aza-spiro[4.5]decan-1-one

HRID 2401118

Reaktionsgleichung

Reaktionsgleichung von HRID 2401118
C[O:2][C:3]([C:5]1([CH2:11][CH2:12][NH:13][C:14]2[C:15]([CH3:31])=[N:16][C:17]([N:20]3[CH2:24][CH2:23][C@@H:22]([N:25]4[CH2:29][CH2:28][CH2:27][C@@H:26]4[CH3:30])[CH2:21]3)=[CH:18][CH:19]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=O.CC(C)([O-])C.[K+]>O1CCCC1>[CH3:31][C:15]1[C:14]([N:13]2[CH2:12][CH2:11][C:5]3([CH2:6][CH2:7][O:8][CH2:9][CH2:10]3)[C:3]2=[O:2])=[CH:19][CH:18]=[C:17]([N:20]2[CH2:24][CH2:23][C@@H:22]([N:25]3[CH2:29][CH2:28][CH2:27][C@@H:26]3[CH3:30])[CH2:21]2)[N:16]=1

Komponenten

4

Edukt 2

HCID 23665647Potassium tert-butoxideHCID 712803374-{2-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester

Produkt 1

HCID 545909852-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-8-oxa-2-aza-spiro[4.5]decan-1-oneAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 4-{2-[2-methyl-6-((2S,3′R)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester (92 mg, 0.21 mmol) in tetrahydrofuran (2 mL) was added 1 M solution of potassium-tert-butoxide in tetrahydrofuran (0.4 mL, 0.4 mmol). The resulting mixture was heated to 60° C. for 3 hours with stirring. The reaction was cooled to rt and then added NaHCO3 (aq) (20 mL), extracted with EtOAc (2×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to afford a crude solid which was then purified by flash column chromatography (5% 7N NH3 in MeOH/CH2Cl2) to provide 16.8 mg (20% yield, two steps) of the title compound as a solid.

Aufarbeitung

  1. temperatureThe reaction was cooled to rt
  2. extractionadded NaHCO3 (aq) (20 mL), extracted with EtOAc (2×20 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a crude solid which
  7. customwas then purified by flash column chromatography (5% 7N NH3 in MeOH/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-2574d340c057450783b98273d7fc3fd9
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796278B2

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