Diethylamine → N-{4-[(3-Chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-diethylamino-2-butenamide

HRID 612083Notes

Reaction equation

Br[CH2:2][CH:3]=[CH:4][C:5](Cl)=[O:6].[NH2:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][C:13]([C:19]#[N:20])=[C:12]2[NH:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=1.[CH:30]([N:33](CC)[CH:34](C)[CH3:35])(C)[CH3:31].C(NCC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[Cl:29][C:24]1[CH:23]=[C:22]([NH:21][C:12]2[C:11]3[C:16](=[CH:17][CH:18]=[C:9]([NH:8][C:5](=[O:6])[CH:4]=[CH:3][CH2:2][N:33]([CH2:34][CH3:35])[CH2:30][CH3:31])[CH:10]=3)[N:15]=[CH:14][C:13]=2[C:19]#[N:20])[CH:27]=[CH:26][C:25]=1[F:28]

Participants

Conditions

Temperature: -78 °C

Procedure

Added 500 μl (4.80 mmol) 4-bromo-but-2-enoyl chloride to a solution of 1.50 g (4.80 mmol) ) 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile and 836 μl (4.80 mmol) N,N-diisopropylethylamine in 50 ml ThF at 0° C. under N2. At 1 hour added the mixture dropwise to 1.26 ml (24 mmol) diethylamine in 11 ml THF chilled to -78° C. Removed dry ice bath after complete addition, and at 2 hours, 45 minutes poured onto a mixture of ice and saturated sodium bicarbonate. Extracted with ethyl acetate, dried organic layer with brine and sodium sulfate, and stripped solvent. Loaded compound onto a column of silica gel, eluted with 35% methanol/ethyl acetate, stripped solvent from desired fractions, and dried in vacuo, giving 292 mg of yellow-orange solid: mass spectrum (electrospray m/e): M+H=452.4, 454.4.

Workup

additionRemoved dry ice bath after complete addition
extractionExtracted with ethyl acetate, dried organic layer with brine and sodium sulfate
washLoaded compound onto a column of silica gel, eluted with 35% methanol/ethyl acetate
customdried in vacuo

Sources & evidence

ORD record: ord-41f3ebc00e1c4d528cddb204ca27f937
Source dataset: uspto-grants-1999_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06002008

Reaction notes

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