Sodium Carbonate → [4-(2-Methoxy-pyrimidin-5-yl)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

HRID 1677155Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1677155
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=1>C1(C)C=CC=CC=1.O.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([N:10]3[CH2:14][CH2:13][CH2:12][C@H:11]3[CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:9])=[CH:4][CH:3]=2)=[CH:31][N:30]=1

Komponenten

8

Edukt 3

HCID 10340Sodium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 11965129Pyrrolidine, 1-(4-bromobenzoyl)-2-(1-pyrrolidinylmethyl)-, (2S)-

Produkt 1

HCID 57980080[4-(2-Methoxy-pyrimidin-5-yl)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanoneAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

Procedure SS: To a stirred solution of (4-bromo-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone (100 mg, 0.297 mmol), sodium carbonate (94.4 mg, 0.890 mmol) and 2-Methoxy-5-pyrimidine boronic acid (230 mg, 1.48 mmol) in toluene (5 ml), water (1 ml) and ethanol (1.5 ml) under nitrogen was added Tetrakis (triphenylphosphine) palladium (0) (34.3 mg, 0.030 mmol). The reaction was then heated to reflux for 48 h. The reaction was allowed to cool and bound to a SCX-2 cartridge (5 g). The cartridge was washed with two cartridge volumes of dimethylformamide and one volume of methanol. The product was eluted using 2M ammonia in methanol. The ammonia/methanol solution was evaporated on a Genevac HT4. The sample was further purified by prep-LCMS. The resulting acetonitrile/water fractions were combined and evaporated using a Genevac to give 51 mg of a colourless oil (47%). MS (ES+) 367.3

Aufarbeitung

  1. temperatureThe reaction was then heated
  2. temperatureto reflux for 48 h
  3. temperatureto cool
  4. washThe cartridge was washed with two cartridge volumes of dimethylformamide and one volume of methanol
  5. washThe product was eluted
  6. customThe ammonia/methanol solution was evaporated on a Genevac HT4
  7. customThe sample was further purified by prep-LCMS
  8. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-901376a3cd5c463f8bd5313f81feb048
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08008301B2

Notizen zur Reaktion

Wird geladen…