Cesium carbonate → (1R,2S)-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-phenylpentan-2-amine

HRID 13102

Reaktionsgleichung

Reaktionsgleichung von HRID 13102
Cl.[NH2:2][C@@H:3]([CH2:12][CH2:13][CH3:14])[C@@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].[Ar].[F:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:31]3[C:26](=[CH:27][C:28](I)=[CH:29][CH:30]=3)[CH:25]=[N:24]2)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)CCC.[Cu]I>[F:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[C:31]3[C:26](=[CH:27][C:28]([O:5][C@H:4]([C:6]4[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:3]([NH2:2])[CH2:12][CH2:13][CH3:14])=[CH:29][CH:30]=3)[CH:25]=[N:24]2)=[CH:21][CH:22]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 592511281-(4-fluorophenyl)-5-iodo-1H-indazoleHCID 86623008argon (1R,2S)-2-amino-1-phenylpentan-1-ol hydrochloride

Produkt 1

HCID 59339774(1R,2S)-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-phenylpentan-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 8008ButyronitrileLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

In a vial under argon (1R,2S)-2-amino-1-phenylpentan-1-ol hydrochloride (91b, 46 mg, 0.21 mmol), 1-(4-fluorophenyl)-5-iodo-1H-indazole (87 mg, 0.26 mmol), copper(I)iodide (8.12 mg, 0.04 mmol) and cesium carbonate (278 mg, 0.85 mmol) were mixed in butyronitrile (0.6 mL). The vial was sealed and heated to 125° C. for 16 h. The mixture was filtered through celite. The celite was washed with ethyl acetate. The collected organic phases were evaporated and the crude product was purified by preparative HPLC. The pure fractions were collected, ethyl acetate and a saturated sodium carbonate were added and the mixture was shaken. The organic layer was separated and the water layer was washed twice with ethyl acetate. The combined organic layers were dried over sodium sulphate and finally evaporated to give the pure product.

Aufarbeitung

  1. customThe vial was sealed
  2. filtrationThe mixture was filtered through celite
  3. washThe celite was washed with ethyl acetate
  4. customThe collected organic phases were evaporated
  5. customthe crude product was purified by preparative HPLC
  6. customThe pure fractions were collected
  7. additionethyl acetate and a saturated sodium carbonate were added
  8. customThe organic layer was separated
  9. washthe water layer was washed twice with ethyl acetate
  10. dry with materialThe combined organic layers were dried over sodium sulphate
  11. customfinally evaporated
  12. customto give the pure product

Quellen und Nachweise

ORD-Eintrag
ord-de25f8a7ec5b4322bcb8649f1d574484
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728030B2

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