(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate → (R)-6-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-2-(piperidin-3-ylamino)pyrimidin-4(3H)-one

HRID 1529426Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529426
[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]C)[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>Br.CC(O)=O>[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[N:19]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]2)[NH:21][C:22](=[O:24])[CH:23]=1

Komponenten

4

Edukt 1

HCID 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 136338250(R)-6-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-2-(piperidin-3-ylamino)pyrimidin-4(3H)-oneAusbeute 22,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 260Hydrogen BromideLösungsmittel

Versuchsvorschrift

A solution of (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (0.17 g, 0.318 mmol) in 33% HBr in HOAc (3 mL) was heated at 90° C. for 14 h. 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)-6-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-2-(piperidin-3-ylamino)pyrimidin-4(3H)-one (30 mg, 22%). MS (ESI, pos. ion) m/z: 422.1 (M+1); 1H-NMR (400 MHz DMSO-d6): δ ppm 11.78 (s, 1H), 8.48 (s, 1H), 8.13 (d, J=2.4 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 7.40-7.47 (m, 1H), 7.18-7.22 (m, 3H), 6.59 (brs, 1H), 6.00 (s, 1H), 3.93 (brs, 1H), 2.57 (s, 2H), 2.90 (d, J=9.2 Hz, 1H), 1.74 (brs, 1H), 1.50-1.53 (m, 2H), 1.18-1.22 (m, 3H).

Aufarbeitung

  1. customThe reaction was quenched with aq. NaHCO3
  2. extractionextracted 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-3cca105d3a624277bea0f26831daf580
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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