5-(6-Hydroxymethyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide → 5-(6-Formyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 45109

Reaktionsgleichung

Reaktionsgleichung von HRID 45109
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[CH:27]=[C:26]([CH2:28][OH:29])[N:25]=[CH:24][N:23]=4)=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1>C(Cl)Cl>[F:30][C:2]([F:1])([F:31])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[CH:27]=[C:26]([CH:28]=[O:29])[N:25]=[CH:24][N:23]=4)=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Komponenten

3

Edukt 1

HCID 593941835-(6-Hydroxymethyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Produkt 1

HCID 866430855-(6-Formyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a suspension of 5-(6-Hydroxymethyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide (310 mg, 0.724 mmol) in DCM (10 mL), DMP (337 mg, 0.795 mmol) is added. The reaction mixture is stirred at rt until complete as seen by LCMS (about 1 h). The reaction is quenched with saturated aqueous NaHCO3 and extracted with EtOAc (3×10 mL). The combined organic layers are then washed by brine, dried (Na2SO4), filtered and concentrated. The crude residue is purified by FCC (0-40% EtOAc/Heptane) to provide the title compound. MS (ESI) m/z 443.1 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.84 (d, J=1.01 Hz, 1 H), 8.36 (d, J=9.09 Hz, 1 H), 8.06 (s, 1 H), 7.96 (d, J=3.79 Hz, 1 H), 7.89 (s, 1 H), 7.55-7.60 (m, 1 H), 7.45 (s, 1 H), 7.40 (d, J=1.01 Hz, 2 H), 7.44 (d, J=2.53 Hz, 1 H), 7.13 (dd, J=8.97, 2.40 Hz, 1 H), 6.76 (d, J=3.79 Hz, 1 H), 2.66 (s, 3 H).

Aufarbeitung

  1. additionis added
  2. customas seen by LCMS (about 1 h)
  3. customThe reaction is quenched with saturated aqueous NaHCO3
  4. extractionextracted with EtOAc (3×10 mL)
  5. washThe combined organic layers are then washed by brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue is purified by FCC (0-40% EtOAc/Heptane)

Quellen und Nachweise

ORD-Eintrag
ord-4ef80e76f6c24436b8e4148b435c5294
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541432B2

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