1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutanecarboxylic acid ethyl ester → 2-methyl-1-(1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutyl)-propan-1-one

HRID 1630936Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1630936
C([O:3][C:4]([C:6]1([CH2:10][NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([C:18]3[N:19]([CH3:27])[C:20]4[C:25]([CH:26]=3)=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:17]=2)[CH2:9][CH2:8][CH2:7]1)=O)C.[CH:28]([Mg]Cl)([CH3:30])[CH3:29]>C1COCC1>[CH3:29][CH:28]([CH3:30])[C:4]([C:6]1([CH2:10][NH:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([C:18]3[N:19]([CH3:27])[C:20]4[C:25]([CH:26]=3)=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:17]=2)[CH2:7][CH2:8][CH2:9]1)=[O:3]

Komponenten

4

Edukt 2

HCID 595346291-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutanecarboxylic acid ethyl esterHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 595346582-methyl-1-(1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutyl)-propan-1-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutanecarboxylic acid ethyl ester (Example 213b, 0.45 g, 1.21 mmol) in THF (150 mL) cooled with an ice-water bath is added iPrMgCl (2.0M in THF, 2.43 mL, 4.85 mmol) dropwise. After 45 min, the mixture is quenched with 1M aqueous NaHSO4 (5 mL), washed with saturated aqueous sodium bicarbonate and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:2 to 1:1), followed by purification by RP HPLC on an Xbridge RP18 eluting with a gradient of acetonitrile in 0.1% aqueous NH4OH to give 2-methyl-1-(1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutyl)-propan-1-one.

Aufarbeitung

  1. customthe mixture is quenched with 1M aqueous NaHSO4 (5 mL)
  2. washwashed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:2 to 1:1)
  7. customfollowed by purification by RP HPLC on an Xbridge
  8. washRP18 eluting with a gradient of acetonitrile in 0.1% aqueous NH4OH

Quellen und Nachweise

ORD-Eintrag
ord-76e40aadec764fd2a7d610bd2f0fa758
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791141B2

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