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

HRID 612094Notes

Reaction equation

HRID 612094 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 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 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-db0c13547d404899b12f192941819643
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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