Citric Acid → [3-(2-tert-Butyl-pyrimidin-4-yl)-6-chloro-1H-indol-5-yl]-[4-(4-fluorobenzyl)-piperidin-1-yl]-methanone

HRID 1891020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1891020
[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11][N:10]([CH:13]=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.C(C1[C:28]2[C:23](=[CH:24][C:25]([Cl:32])=[C:26](C(O)=O)[CH:27]=2)[NH:22][CH:21]=1)(=O)C.[C:33]([N:40]1[CH:44]=[CH:43]N=C1)([N:35]1[CH:39]=[CH:38]N=C1)=O.Cl.FC1C=[CH:58][C:50]([CH2:51]C2CCNCC2)=[CH:49]C=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C(N(CC)CC)C>[C:50]([C:33]1[N:35]=[C:39]([C:38]2[C:28]3[C:23](=[CH:24][C:25]([Cl:32])=[C:26]([C:13]([N:10]4[CH2:11][CH2:12][CH:7]([CH2:6][C:5]5[CH:15]=[CH:16][C:2]([F:1])=[CH:3][CH:4]=5)[CH2:8][CH2:9]4)=[O:14])[CH:27]=3)[NH:22][CH:21]=2)[CH:43]=[CH:44][N:40]=1)([CH3:58])([CH3:51])[CH3:49]

Komponenten

8

Edukt 5

HCID 311Citric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 170394924-[(4-Fluorophenyl)methyl]piperidine hydrochlorideHCID 677727683-acetyl-6-chloro-1H-indole-5-carboxylic acidHCID 86666103[4-(4-Fluorobenzyl)piperidin-1-yl]methanone

Produkt 1

HCID 57325406[3-(2-tert-Butyl-pyrimidin-4-yl)-6-chloro-1H-indol-5-yl]-[4-(4-fluorobenzyl)-piperidin-1-yl]-methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

Preparation of 3-acetyl-6-chloro-1H-indol-5-yl)[4-(4-fluorobenzyl)piperidin-1-yl]methanone. A mixture of 3-acetyl-6-chloro-1H-indole-5-carboxylic acid (0,098 g, 0.41 mmol) and carbonyldiimidazole (0.101 g, 0.62 mmol) in dimethylformamide (1.0 mL) was stirred at room temperature for 1.5 h under nitrogen. The reaction mixture was cooled in ice bath, added 4-(4-fluorobenzyl)piperidine hydrochloride (0.1 g, 0.45 mmol), and triethylamine (0.5 g). The resulting mixture was stirred at room temperature for 3 h under nitrogen, added 5% citric acid and extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with water, dried (MgSO4) and concentrated to dryness. The residue was purified by silica gel flash chromatography using 25% ethyl acetate in heptane to afford the title compound as a glassy substance (0.08 g, 47%), m/z 413 (M+H).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled in ice bath
  2. stirringThe resulting mixture was stirred at room temperature for 3 h under nitrogen
  3. extractionextracted with ethyl acetate (2×10 mL)
  4. washThe combined organic extracts were washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by silica gel flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-6268938d990645748d760bbccc2e6afa
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08507499B2

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