1-(2-Imidazol-1-yl-ethyl)-piperazine → 6-Methoxyquinoline-3-carbonitrile

HRID 499121Notes

Reaction equation

ClC1C=C(N[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])C=CC=1SC1N(C)C=CN=1.N1(CCN2CCNCC2)C=CN=C1>CN1CCCC1=O>[CH3:27][O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]([C:29]#[N:30])=[CH:16]2

Participants

Conditions

Temperature: 105 °C

Procedure

Following the procedure of Example 11, a mixture of 220 mg (0.5 mmol) of 4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)-phenylamino]-7-fluoro-6-methoxyquinoline-3-carbonitrile and 290 mg (1.6 mmol) of 1-(2-imidazole-1-yl-ethyl)piperazine in 1.2 mL of 1-methyl 2-pyrrolidinone is heated at 105° C. for 20 hours to yield the crude product. Purification by silica gel chromatography (gradient 95:5-methylene chloride/methanol to 85:15 methylene chloride/methanol) gives 210 mg of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-7-{4-[2-1H-imidazole-1-yl)ethyl]piperazin-1-yl}-6-methoxyquinoline-3-carbonitrile as a beige solid, mp 251-253° C.

Workup

customto yield the crude product
customPurification by silica gel chromatography (gradient 95:5-methylene chloride/methanol to 85:15 methylene chloride/methanol)

Sources & evidence

ORD record: ord-8b21cf1ed9bd4fceb2bfaefbf77ef585
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07767671B2

Reaction notes

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