N-methyl-2-pyrrolidone → 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile

HRID 269767Notes

Reaction equation

HRID 269767 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22](F)=[CH:23][CH:24]=3)[N:19]=[CH:18][C:17]=2[C:27]#[N:28])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1.[CH3:29][N:30]1[CH2:34][CH2:33][CH2:32][C:31]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:29]([N:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)[CH2:3][CH2:4]4)=[CH:23][CH:24]=3)[N:19]=[CH:18][C:17]=2[C:27]#[N:28])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 684601654-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl)amino)-7-fluoroquinoline-3-carbonitrile

Product 1

HCID 684605544-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile

Conditions

Temperature
105 °C

Procedure

Following the procedure of Example 11, a mixture of 150 mg (0.37 mmol) of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-7-fluoroquinoline-3-carbonitrile and 339 mg (2.20 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 9:1 methylene chloride/methanol) gives 66 mg of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile as a yellow solid, mp 125-130° C.

Workup

  1. customto yield the crude product
  2. customPurification by silica gel chromatography (gradient 98:2 methylene chloride/methanol to 9:1 methylene chloride/methanol)

Sources & evidence

ORD record
ord-884285f128be4f5bae78b0fde03b97ea
Source dataset
uspto-grants-2008_11
Patent number
US07449460B2

Reaction notes

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