Cesium carbonate → 3-[6-(6-Methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-azetidine-1-carboxylic acid tert-butyl ester trifluoroacetate

HRID 242330Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 242330
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[C:14]3[CH2:22][NH:21][CH2:20][CH2:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:24]1[CH:25]=[C:26]([C:32]([F:35])([F:34])[F:33])[C:27]([O:30][CH3:31])=[N:28][CH:29]=1.[C:36](=[O:39])([O-])[O-:37].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:33][C:32]([F:35])([F:34])[C:36]([OH:37])=[O:39].[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[C:14]3[CH2:22][N:21]([C:24]4[CH:29]=[N:28][C:27]([O:30][CH3:31])=[C:26]([C:32]([F:35])([F:34])[F:33])[CH:25]=4)[CH2:20][CH2:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 533931825-Bromo-2-methoxy-3-(trifluoromethyl)pyridineHCID 574953433-(5,6,7,8-Tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 866631203-[6-(6-Methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-azetidine-1-carboxylic acid tert-butyl ester trifluoroacetateAusbeute 174 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a glass vial was added 3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl ester (110 mg, 0.359 mmol), 5-Bromo-2-methoxy-3-(trifluoromethyl)pyridine (92 mg, 0.359 mmol), cesium carbonate (234 mg, 0.718 mmol), tris(dibenzylideneacetone)dipalladium(0) (33 mg, 0.036 mmol), X-Phos (58 mg, 0.122 mmol) and anhydrous dioxane (2.0 mL). The vial was flushed with a stream of argon for 15 sec and capped. The mixture was heated with stirring for 1.5 h at 110° C. and then stirred at room temperature for 18 h. Diluted with CH2Cl2 (50 mL), filtered through a celite pad and concentrated in vacuo. Purified by reverse phase Gilson HPLC (Method A) to give the 3-[6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy]-azetidine-1-carboxylic acid tert-butyl ester trifluoroacetate as a brown gum (186 mg, 87% yield) LCMS: [M+H]+=482.3, Rt(7)=1.56 min.

Aufarbeitung

  1. customThe vial was flushed with a stream of argon for 15 sec
  2. customcapped
  3. temperatureThe mixture was heated
  4. stirringstirred at room temperature for 18 h
  5. additionDiluted with CH2Cl2 (50 mL)
  6. filtrationfiltered through a celite pad
  7. concentrationconcentrated in vacuo
  8. customPurified by reverse phase Gilson HPLC (Method A)

Quellen und Nachweise

ORD-Eintrag
ord-5401d221058c42f1a6034ce909d8bbbd
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653092B2

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