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

HRID 1935009Notes

Reaction equation

HRID 1935009 reaction equation
[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].CN1CCOCC1.ClC(OCC(C)C)=O.[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]([S:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[C:38]([Cl:49])[CH:37]=1>C1COCC1.CN(C=O)C>[Cl:49][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[S:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 685352-Butynoic acidHCID 1317214936-Amino-4-[(3-chloro-4thiophenoxyphenyl)amino]-3-quinolinecarbonitrile

Product 1

HCID 131721492N-{4-[(3-Chloro-4-thiophenoxyphenyl)amino]-3-cyano-6quinolinyl}-2-butynamideYield 24.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Dissolved 314 mg (3.72 mmol) 2-butynoic acid in 40 ml THF under N2. Chilled to 0° and added 409 μl (3.72 mmol) N-methylmorpholine and 485 μl (3.72 mmol) isobutyl chloroformate and stirred for 10 minutes. Added dropwise a solution that was prepared by dissolving 1.00 g (2.48 mmol) 6-amino-4-[(3-chloro-4-thiophenoxyphenyl)amino]-3-quinolinecarbonitrile in 2.0 ml hot DMF and adding 20 ml THF. Stirred mixture for 15 minutes at 0° and 25° C. overnight. To drive reaction to completion, added 1.24 mmol of the mixed anhydride (104 mg acid, 136 μl NMM, and 161 μl isobutyl chloroformate) in 15 ml THF. Stirred overnight. Stripped solvent, dried in vacuo. Recrystallized from ethyl acetate, dried in vacuo, giving 284 mg of yellow-orange solid: mass spectrum (electrospray m/e): M+H=469.2, 471.2.

Workup

  1. temperatureChilled to 0°
  2. additionAdded dropwise a solution that
  3. customwas prepared
  4. stirringStirred mixture for 15 minutes at 0°
  5. custom25° C. overnight
  6. customreaction to completion
  7. stirringStirred overnight
  8. customdried in vacuo
  9. customRecrystallized from ethyl acetate
  10. customdried in vacuo

Sources & evidence

ORD record
ord-cafe46f0269746e5a1ee392952abcd2f
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

Loading…