Hydrochloric Acid → (R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine

HRID 1529425Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529425
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]2)[N:19]=1.Cl>O1CCOCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]2)[N:19]=1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 67959910(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate

Produkt 1

HCID 67959825(R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amineAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To solution of (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (130 mg, 0.243 mmol) in dioxane (2 mL) was added HCl in dioxane (4 M, 2 mL) and the mixture was heated at 90° C. for overnight. The reaction was quenched with aq.NaHCO3 and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was washed with 50% EtOAc in petroleum ether to give (R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine (22 mg, 22%). MS (ESI, pos. ion) m/z: 436.1 (M+1); 1H-NMR (400 MHz DMSO-d6): δ ppm: 11.78 (brs, 1H) 8.66 (s, 1H), 8.25 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.41-7.46 (m, 1H), 7.21-7.22 (m, 3H), 6.70 (s, 1H), 6.48 (s, 1H), 3.80-3.83 (brs, 4H), 2.89-2.99 (m, 1H), 2.33-2.41 (m, 2H), 1.98-1.99 (m, 2H), 1.43-1.50 (m, 2H), 1.12-1.24 (m, 2H).

Aufarbeitung

  1. customThe reaction was quenched with aq
  2. extractionNaHCO3 and extracted with EtOAc
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washThe residue was washed with 50% EtOAc in petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-e90774d126fa47fcb47e3575745769b3
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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