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

HRID 1935024Notes

Reaction equation

HRID 1935024 reaction equation
Br[CH2:2][CH:3]=[CH:4][C:5]([O:7][Si](C)(C)C)=O.C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[N:25]=[CH:24][C:23]([C:29]#[N:30])=[C:22]2[NH:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[C:34]([Br:39])[CH:33]=1.[CH:40]([N:43](CC)[CH:44](C)C)(C)C.CNC.C(=O)(O)[O-].[Na+]>CN(C=O)C.C1COCC1.C(Cl)Cl>[Br:39][C:34]1[CH:33]=[C:32]([NH:31][C:22]2[C:21]3[C:26](=[CH:27][CH:28]=[C:19]([NH:18][C:5](=[O:7])[CH:4]=[CH:3][CH2:2][N:43]([CH3:44])[CH3:40])[CH:20]=3)[N:25]=[CH:24][C:23]=2[C:29]#[N:30])[CH:37]=[CH:36][C:35]=1[F:38]

Participants

10

Reactant 6

HCID 674DimethylamineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 224666726-Amino-4-[(3-bromo-4-fluorophenyl)amino]-3-quinolinecarbonitrileHCID 53861946Trimethylsilyl 4-bromobut-2-enoate

Product 1

HCID 54147240N-{4-[(3-Bromo-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-dimethylamino-2-butenamideYield 36.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Made 2.25 mmol of 5-bromo-but-2-enoyl chloride by mixing 386 μl (2.25 mmol) trimethylsilyl 4-bromo-but-2-enoate, 10 ml methylene chloride, 294 μl (3.38 mmol) oxalyl chloride, and 2 drops of DMF. After bubbling had subsided, removed solvent and dissolved in 10 ml THF. This solution was added to a mixture of 800 mg (2.25 mmol) 6-amino-4-[(3-bromo-4-fluorophenyl)amino]-3-quinolinecarbonitrile, 50 ml THF, and 392 μl (2.25 mmol) N,N-diisopropylethylamine chilled to 0° C. under N2. At 1 hour, added dropwise to a solution of 5.62 ml of 2.0M dimethyl amine in THF (11.2 mmol) at −78° C. Removed dry ice bath after complete addition. After 2 hours, poured into a cold solution of sodium bicarbonate, extracted with ethyl acetate, dried organic layer with sodium sulfate and reduced solvent to a small volume. Loaded onto a column of silica gel and eluted with 50% methanol/ethyl acetate. Stripped solvent of desired fractions and dried in vacuo, giving 386 mg of yellow solid: mass spectrum (electrospray m/e): M+H=467.9, 469.9.

Workup

  1. customAfter bubbling
  2. customremoved solvent
  3. dissolutiondissolved in 10 ml THF
  4. additionRemoved dry ice bath after complete addition
  5. waitAfter 2 hours
  6. extractionextracted with ethyl acetate, dried organic layer with sodium sulfate
  7. washeluted with 50% methanol/ethyl acetate
  8. customdried in vacuo

Sources & evidence

ORD record
ord-d62f711714ec41b6a3212b5e979ef23e
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

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