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

HRID 612082Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=1.[CH:23]([N:26]([CH2:30][CH3:31])[CH:27](C)C)(C)C.BrCC=[CH:35][C:36](Cl)=[O:37].CNC.C(=O)(O)[O-].[Na+]>C1COCC1>[Cl:22][C:17]1[CH:16]=[C:15]([NH:14][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:36](=[O:37])[CH:35]=[CH:31][CH2:30][N:26]([CH3:23])[CH3:27])[CH:3]=3)[N:8]=[CH:7][C:6]=2[C:12]#[N:13])[CH:20]=[CH:19][C:18]=1[F:21]

Participants

Conditions

Temperature: 0 °C

Procedure

Dissolved 1.50 g (4.80 mmol) 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile in 50 ml THF, added 836 μl (4.80 mmol) N,N-diisopropylethylamine, and chilled to 0° C. under N2. Added 500 μl (4.80 mmol) 4-bromo-but-2-enoyl chloride and after 1 hour dropwise added the mixture to 10 ml of a 2M solution (19 mmol) of dimethylamine in THF cooled to -78° C. At 2 hours, added 5 ml (9.5 mmol) more of dimethyl amine solution and warmed to 25° C. After 1 hour, poured onto a cold solution of sodium bicarbonate. Extracted with ethyl acetate, dried organics with brine and sodium sulfate, reduced to small volume and loaded onto a column of silica gel. Eluted with 70% methanol/ethyl acetate, stripped solvent of desired fractions and dried in vacuo, giving 427 mg of yellow solid: mass spectrum (electrospray m/e): M+H=424.0, 426.0.

Workup

temperaturecooled to -78° C
temperaturewarmed to 25° C
waitAfter 1 hour
extractionExtracted with ethyl acetate, dried organics with brine and sodium sulfate
washEluted with 70% methanol/ethyl acetate
customdried in vacuo

Sources & evidence

ORD record: ord-5a8207d705eb45919d8822ffcb8299e4
Source dataset: uspto-grants-1999_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06002008

Reaction notes

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