5-(6-Formyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide → (+/-)-5-[6-(1-Hydroxy-ethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 45108

Reaktionsgleichung

Reaktionsgleichung von HRID 45108
[CH3:1][Mg]Br.[F:4][C:5]([F:34])([F:33])[C:6]1[CH:7]=[C:8]([NH:12][C:13]([N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][C:25]4[CH:30]=[C:29]([CH:31]=[O:32])[N:28]=[CH:27][N:26]=4)=[CH:21][CH:22]=3)[CH:17]=[CH:16]2)=[O:14])[CH:9]=[CH:10][CH:11]=1>C1COCC1>[F:34][C:5]([F:33])([F:4])[C:6]1[CH:7]=[C:8]([NH:12][C:13]([N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][C:25]4[CH:30]=[C:29]([CH:31]([OH:32])[CH3:1])[N:28]=[CH:27][N:26]=4)=[CH:21][CH:22]=3)[CH:17]=[CH:16]2)=[O:14])[CH:9]=[CH:10][CH:11]=1

Komponenten

4

Edukt 2

HCID 866430855-(6-Formyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amideHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 59394390(+/-)-5-[6-(1-Hydroxy-ethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Methylmagnesium bromide solution (3 M in ether, 20 mL) is added to a solution of 5-(6-formyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide (5.0 g 11.7 mmol) in THF (400 mL) at 0° C. The mixture is stirred at that temperature for 3 h before the reaction is then quenched with saturated aqueous NH4Cl. The product is extracted with EtOAc (3×40 mL) and the combined organic layers are washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue is purified semi-prep HPLC (018; 30-100% I/H2O with 0.1% TFA) to give the title compound as a racemate. MS (EST) m/z 441.1 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.62 (s, 1 H), 8.36 (d, J=8.84 Hz, 1 H), 8.06 (s, 1 H), 7.95 (d, J=3.79 Hz, 1 H), 7.90 (d, J=8.08 Hz, 1 H), 7.58 (t, J=7.83 Hz, 1 H), 7.43 (d, J=2.27 Hz, 2 H), 7.12 (dd, J=8.97, 2.40 Hz, 1 H), 7.09 (s, 1 H), 6.75 (d, J=3.79 Hz, 1 H), 4.75 (d, J=6.57 Hz, 1 H), 1.45 (d, J=6.57 Hz, 3 H).

Aufarbeitung

  1. customis then quenched with saturated aqueous NH4Cl
  2. extractionThe product is extracted with EtOAc (3×40 mL)
  3. washthe combined organic layers are washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified semi-prep HPLC (018; 30-100% I/H2O with 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-3f4e5fa381054a29b36fef0125c5ce27
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541432B2

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