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

HRID 1842748

Reaktionsgleichung

Reaktionsgleichung von HRID 1842748
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[Cl:8][C:9]1[C:10]([C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH3:37])[CH:29]=2)=[N:11][C:12]([NH:15][C:16]2[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[C:19](F)=[CH:18][C:17]=2[O:26][CH3:27])=[N:13][CH:14]=1>FC(F)(F)CO>[Cl:8][C:9]1[C:10]([C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH3:37])[CH:29]=2)=[N:11][C:12]([NH:15][C:16]2[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[C:19]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:18][C:17]=2[O:26][CH3:27])=[N:13][CH:14]=1

Komponenten

4

Edukt 2

HCID 531671-MethylpiperazineHCID 712392825-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 712408915-chloro-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amineAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 64092,2,2-TrifluoroethanolLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

1-Methylpiperazine (0.50 mL, 4.51 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 87, 750 mg, 1.75 mmol) in 2,2,2-trifluoroethanol (15 mL) and the mixture was heated in a microwave at 120° C. for 1 h and then 140° C. for 0.5 h. The mixture was then concentrated in vacuo and the residue was dissolved in EtOAc (100 mL). This organic solution was washed with sat. NaHCO3 (100 mL), water (2×100 mL) and then brine (100 mL). The solution was then dried (MgSO4) and concentrated in vacuo onto silica. Purification by FCC, eluting with 0-4% CH3OH in CH2Cl2 gave the title compound (772 mg, 87%) as a orange solid; 1H NMR: (CDCl3) 2.37 (3H, s), 2.59-2.65 (4H, m), 3.07-3.14 (4H, m), 3.90 (3H, s), 3.99 (3H, s), 6.63 (1H, s), 7.25-7.3 (1H, m) partially obscured by chloroform peak, 7.31-7.36 (1H, m), 7.39 (1H, d), 7.56 (1H, s), 8.22 (1H, s), 8.39 (1H, s), 8.47 (1H, d), 9.18 (1H, s); m/z: ES+ MH+ 508.19.

Aufarbeitung

  1. concentrationThe mixture was then concentrated in vacuo
  2. dissolutionthe residue was dissolved in EtOAc (100 mL)
  3. washThis organic solution was washed with sat. NaHCO3 (100 mL), water (2×100 mL)
  4. dry with materialThe solution was then dried (MgSO4)
  5. concentrationconcentrated in vacuo onto silica
  6. customPurification by FCC
  7. washeluting with 0-4% CH3OH in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-50f2520b97ac40c191c408d41a7e4bfe
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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