N-methyl-2-pyrrolidone → 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-ethoxy-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile
Reaktionsgleichung
[Cl:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22](F)=[C:23]([O:26][CH2:27][CH3:28])[CH:24]=3)[N:19]=[CH:18][C:17]=2[C:30]#[N:31])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1.[CH3:32][N:33]1[CH2:37][CH2:36][CH2:35][C:34]1=O>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([N:15]4[CH2:16][CH2:17][CH:32]([N:33]5[CH2:37][CH2:36][CH2:35][CH2:34]5)[CH2:3][CH2:4]4)=[C:23]([O:26][CH2:27][CH3:28])[CH:24]=3)[N:19]=[CH:18][C:17]=2[C:30]#[N:31])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1Komponenten
3
Edukt 2
Produkt 1
Reaktionsbedingungen
- Temperatur
- 105 °C
Versuchsvorschrift
Following the procedure of Example 11, a mixture of 150 mg (0.33 mmol) of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]phenyl}amino)-6-ethoxy-7-fluoro-3-quinolinecarbonitrile and 306 mg (1.98 mmol) of 4-(1-pyrrolidinylpiperidine) in 1 mL of 1-methyl 2-pyrrolidinone is heated at 105° C. for 17 hours to yield the crude product. Purification by silica gel chromatography (gradient 98:2 methylene chloride/methanol to 4:1 methylene chloride/methanol) gives 122 mg of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-ethoxy-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile as a yellow solid, mp 203-207° C.