Sodium Methoxide → (R)-N-{4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}quinuclidine-3-amine

HRID 1925214Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1925214
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([NH:10][C:11]([NH2:13])=[NH:12])[CH2:3]2.C[O-].[Na+].CN(C)[CH:19]=[CH:20][C:21]([C:23]1[N:30]2[C:26]([O:27][CH:28]=[CH:29]2)=[N:25][C:24]=1[C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)=O>C(O)C>[F:37][C:34]1[CH:33]=[CH:32][C:31]([C:24]2[N:25]=[C:26]3[N:30]([C:23]=2[C:21]2[CH:20]=[CH:19][N:13]=[C:11]([NH:10][C@@H:4]4[CH:5]5[CH2:6][CH2:7][N:2]([CH2:9][CH2:8]5)[CH2:3]4)[N:12]=2)[CH:29]=[CH:28][O:27]3)=[CH:36][CH:35]=1

Komponenten

5

Edukt 3

HCID 10942334Sodium MethoxideHCID 675198943-(Dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-oneHCID 178479392HCID 178479392, Verbindung

Produkt 1

HCID 16726810(R)-N-{4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}quinuclidine-3-amineAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

A 5 L 3-neck round bottom flask is charged with the N-1-azabicyclo[2.2.2]oct-3-ylguanidine hydrochloride (261.5 g, 1.277 mol) and absolute ethanol. Sodium methoxide (21% by weight) (405 ml, 1.08 mol) is added dropwise over 15 min. The 3-(dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-one (232.1 g, 0.776 mol) is then added in portions so that no reaction mixture temperature change is observed. The reaction mixture is then refluxed for 5 hours and cooled to room temperature. Solvent is removed in vacuo and the residue partitioned between 1N NaOH and ethyl acetate. The resulting solids are filtered, washed with water, ethyl acetate, and then dried. The solids are then mostly dissolved in hot isopropyl alcohol and filtered through celite while hot. The isopropyl alcohol solution is concentrated to dryness and the solids dried under vacuum to give the desired pyrimidine compound (143.8 g) as a tan solid in 46% yield.

Aufarbeitung

  1. temperatureThe reaction mixture is then refluxed for 5 hours
  2. customSolvent is removed in vacuo
  3. customthe residue partitioned between 1N NaOH and ethyl acetate
  4. filtrationThe resulting solids are filtered
  5. washwashed with water, ethyl acetate
  6. customdried
  7. dissolutionThe solids are then mostly dissolved in hot isopropyl alcohol
  8. filtrationfiltered through celite while hot
  9. concentrationThe isopropyl alcohol solution is concentrated to dryness
  10. customthe solids dried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-480894900f1944e3888a0b59ddb4e7f8
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178672B2

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