4-Chlorobenzylamine → (4-Chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine

HRID 1186513Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1186513
CS([C:5]1[N:10]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)[C:14]3=[N:13][CH:12]=2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1>>[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH:33][C:5]2[N:10]=[C:9]([C:11]3[N:15]4[CH:16]=[CH:17][N:18]=[C:19]([N:20]5[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]5)[C:14]4=[N:13][CH:12]=3)[CH:8]=[CH:7][N:6]=2)=[CH:30][CH:29]=1

Komponenten

3

Edukt 2

HCID 660364-ChlorobenzylamineHCID 682264863-(2-Methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine

Produkt 1

HCID 66548825(4-Chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

The mixture of 3-(2-methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 46 supra) (150 mg, 0.402 mmol) and 4-chlorobenzylamine (228 mg, 1.608 mmol) was heated at 140° C. with stirring for 2 hours. The oil was purified by chromatography (silica gel, 10 g, 200˜300 mesh, eluting with dichloromethane:methanol, 30:1˜10:1) to afford the crude product (100 mg). The crude product was purified by prep-HPLC. Several drops of concentrated HCl were added to the fractions with product. After sonicating for several minutes, solution was concentrated under reduced pressure to afford (4-chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine; hydrochloride. (Yield 38 mg, 21.8%). 1H NMR (300 MHz, CDCl3): δ 8.68 (s, 1H), 8.28 (s, 1H), 7.53 (d, 1H, J=6.9 Hz), 7.38-7.29 (m, 6H), 5.48-5.43 (m, 2H), 4.76 (brs, 2H), 3.68-3.61 (m, 4H), 3.34-3.27 (m, 4H), 2.89 (s, 3H). LC-MS: [M+H]+ 435.

Aufarbeitung

  1. customThe oil was purified by chromatography (silica gel, 10 g, 200˜300 mesh, eluting with dichloromethane:methanol, 30:1˜10:1)
  2. customto afford the crude product (100 mg)
  3. customThe crude product was purified by prep-HPLC
  4. additionSeveral drops of concentrated HCl were added to the fractions with product
  5. customAfter sonicating for several minutes
  6. concentrationsolution was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-5741ae54c454406190b290f0c0436ce0
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673905B2

Notizen zur Reaktion

Wird geladen…