4-Methylmorpholine → N-{4-[(3-Chloro-4-fluoro-phenyl)amino]-3-cyano-6-quinolinyl}-2-butynamide

HRID 1934995Notes

Reaction equation

HRID 1934995 reaction equation
[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[CH:28][C:27]([C:33]#[N:34])=[C:26]2[NH:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[C:38]([Cl:43])[CH:37]=1>C1COCC1>[Cl:43][C:38]1[CH:37]=[C:36]([NH:35][C:26]2[C:25]3[C:30](=[CH:31][CH:32]=[C:23]([NH:22][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:24]=3)[N:29]=[CH:28][C:27]=2[C:33]#[N:34])[CH:41]=[CH:40][C:39]=1[F:42]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 685352-Butynoic acidHCID 110124336-Amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile

Product 1

HCID 22466664N-{4-[(3-Chloro-4-fluoro-phenyl)amino]-3-cyano-6-quinolinyl}-2-butynamideYield 24.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dissolved 336 mg (4.00 mmol) 2-butynoic acid in 20 ml of THF and chilled to 0° C. under N2. Added 520 μl (4.00 mmol) isobutyl chloroformate and 440 μl (4.00 mmol) N-methylmorpholine and stirred for 10 minutes. Added a solution of 500 mg (1.60 mmol) 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile, stirred for 15 minutes at 0° C. and then at 25° C. overnight. Stripped solvent, washed with water, collected and dried in vacuo. Recrystallized from ethyl acetate, giving 148 mg of a yellow solid: mass spectrum (electrospray m/e): M+H=379.1, 381.1.

Workup

  1. stirringstirred for 15 minutes at 0° C.
  2. customat 25° C.
  3. customovernight
  4. washwashed with water
  5. customcollected
  6. customdried in vacuo
  7. customRecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-294c707366b34951a320a5606822467a
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

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