N-methyl-2-pyrrolidone → 4-[3-Chloro-4-(pyridin-2-ylsulfanyl)-phenylamino]-6-methoxy-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinoline-3-carbonitrile

HRID 269765Notes

Reaction equation

HRID 269765 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)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][C:17]=2[C:29]#[N:30])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.[CH3:31][N:32]1[CH2:36][CH2:35][CH2:34][C:33]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:10]4[CH2:11][CH2:12][CH:31]([N:32]5[CH2:36][CH2:35][CH2:34][CH2:33]5)[CH2:14][CH2:9]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][C:17]=2[C:29]#[N:30])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 684606534-[3-Chloro-4-(pyridin-2-ylsulfanyl)-phenylamino]-7-fluoro-6-methoxyquinoline-3-carbonitrile

Product 1

HCID 684608654-[3-Chloro-4-(pyridin-2-ylsulfanyl)-phenylamino]-6-methoxy-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinoline-3-carbonitrile

Procedure

Following the procedure of Example 11, a mixture of 150 mg (0.34 mmol) of 4-[3-Chloro-4-(pyridin-2-ylsulfanyl)-phenylamino]-7-fluoro-6-methoxyquinoline-3-carbonitrile and 264 mg (1.71 mmol) of 4-(1-pyrrolidinylpiperidine) are refluxed in 1-methyl 2-pyrrolidinone (1 mL) at 105° C. for 12 hours to yield the crude product. Purification by silica gel chromatography (95:5 methylene chloride/methanol) gives 126 mg of 4-[3-chloro-4-(pyridin-2-ylsulfanyl)-phenylamino]-6-methoxy-7-(4-pyrrolidin-1-yl-piperidin-1-yl)quinoline-3-carbonitrile as a yellow solid, mp 203-205° C.

Workup

  1. customto yield the crude product
  2. customPurification by silica gel chromatography (95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-831a888231ac405f98afd0207cda2c92
Source dataset
uspto-grants-2008_11
Patent number
US07449460B2

Reaction notes

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