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

HRID 612084Notes

Reaction equation

HRID 612084 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.C(N(CC)C(C)C)(C)C.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.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:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[CH:10]=3)[N:15]=[CH:14][C:13]=2[C:19]#[N:20])[CH:27]=[CH:26][C:25]=1[F:28]

Participants

7

Reactant 5

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 110124336-Amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrileHCID 536352004-Bromo-but-2-enoyl chloride

Product 1

HCID 54369869N-{4-[(3-Chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-morpholino-2-butenamideYield 35.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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 2.09 ml (24 mmol) morpholine in 10 ml THF at 0° C. Removed ice bath upon complete addition and at 3 hours, poured reaction 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 12% methanol/ethyl acetate, stripped solvent from desired fractions, and dried in vacuo, giving 798 mg of yellow solid: mass spectrum (electrospray m/e): M+H=466.4, 468.4.

Workup

  1. additionRemoved ice bath upon complete addition
  2. additionpoured
  3. customreaction
  4. extractionExtracted with ethyl acetate, dried organic layer with brine and sodium sulfate
  5. washLoaded compound onto a column of silica gel, eluted with 12% methanol/ethyl acetate
  6. customdried in vacuo

Sources & evidence

ORD record
ord-ef1e7be2006f4ae49a7482b88339fd49
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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