1-Methylpiperazine → N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine

HRID 1842735

Reaktionsgleichung

Reaktionsgleichung von HRID 1842735
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.F[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:12]([NH:18][C:19]2[N:24]=[C:23]([C:25]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:27]([CH3:34])[CH:26]=3)[C:22]([CH3:35])=[CH:21][N:20]=2)=[C:11]([O:36][CH3:37])[CH:10]=1>FC(F)(F)CO.C(O)C>[CH3:37][O:36][C:11]1[CH:10]=[C:9]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:12]=1[NH:18][C:19]1[N:24]=[C:23]([C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([CH3:34])[CH:26]=2)[C:22]([CH3:35])=[CH:21][N:20]=1

Komponenten

5

Edukt 2

HCID 531671-MethylpiperazineHCID 71239199N-(4-fluoro-2-methoxy-5-nitrophenyl)-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 71240823N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amineAusbeute 62,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 64092,2,2-TrifluoroethanolLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

1-Methylpiperazine (0.453 mL, 4.08 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 79, 554 mg, 1.36 mmol) in 2,2,2-trifluoroethanol (10 mL). The mixture was heated in a microwave at 120° C. for 1 h. The mixture was then concentrated in vacuo and the residue was dissolved in CH2Cl2 (50 mL). This solution was washed water (2×50 mL) and sat. brine (50 mL), then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-10% CH3OH in CH2Cl2 gave an orange gum. This gum was dissolved in ethanol (25 mL) and a solid precipitated. This solid was collected by filtration and washed with ethanol to give the title compound (413 mg, 62%) as a yellow/orange solid; 1H NMR: 2.25 (3H, s), 2.39 (3H, s), 2.45-2.54 (4H, m), 3.03-3.10 (4H, m), 3.91 (3H, s), 3.98 (3H, s), 6.86 (1H, s), 7.06 (1H, dd), 7.22-7.28 (1H, m), 7.51 (1H, d), 8.02 (1H, s), 8.07 (1H, s), 8.26-8.30 (1H, m), 8.38 (1H, d), 8.69 (1H, s); m/z: ES+ MH+ 488.29.

Aufarbeitung

  1. concentrationThe mixture was then concentrated in vacuo
  2. dissolutionthe residue was dissolved in CH2Cl2 (50 mL)
  3. washThis solution was washed water (2×50 mL) and sat. brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by FCC
  7. washeluting with 1-10% CH3OH in CH2Cl2
  8. customgave an orange gum
  9. customa solid precipitated
  10. filtrationThis solid was collected by filtration
  11. washwashed with ethanol

Quellen und Nachweise

ORD-Eintrag
ord-5c632593939345169284296958909abe
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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