Sodium Hydroxide → (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate

HRID 1529424Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529424
[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)[N:14](S(C1C=CC(C)=CC=1)(=O)=O)[CH:13]=[C:12]2[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[N:31]=[C:30]([NH:36][C@@H:37]2[CH2:42][CH2:41][CH2:40][N:39]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38]2)[N:29]=1.[OH-].[Na+]>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:28]1[CH:33]=[C:32]([O:34][CH3:35])[N:31]=[C:30]([NH:36][C@@H:37]2[CH2:42][CH2:41][CH2:40][N:39]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38]2)[N:29]=1

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 67959888(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate

Produkt 1

HCID 67959910(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylateAusbeute 77,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (500 mg, 0.726 mmol) in dioxane (7 mL) was added 7M aq.NaOH (7 mL) and the mixture was heated at 90° C. for 6 h. The reaction was quenched with water and the suspension was filtered. The resulting solid was washed with water and dried. The crude product was purified with silica gel chromatography (eluting with 50% EtOAc in Hexanes) to give (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (300 mg, 77%). MS (ESI, pos. ion) m/z: 536.0 (M+1); 1H-NMR (400 MHz CDCl3): δ ppm: 8.63 (s, 1H), 8.41 (brs, 1H), 7.90 (s, 1H), 7.65-7.77 (m, 1H), 7.48-7.57 (m, 2H), 7.30-7.35 (m, 1H), 6.99-7.03 (m, 2H), 6.43 (s, 1H), 5.00 (s, 1H), 4.09-4.13 (m, 1H), 3.92 (s, 3H), 3.33-3.73 (m, 4H), 2.05 (s, 1H), 1.63-1.72 (m, 1H), 1.38 (s, 9H), 0.86-0.90 (m, 1H).

Aufarbeitung

  1. customThe reaction was quenched with water
  2. filtrationthe suspension was filtered
  3. washThe resulting solid was washed with water
  4. customdried
  5. customThe crude product was purified with silica gel chromatography (eluting with 50% EtOAc in Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-70bf98da246640d3b8adb24e6dccfb5d
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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