4-Methylmorpholine → N-[4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl]-2-butynamide

HRID 611978Notes

Reaction equation

HRID 611978 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][C:32]=1[O:33][CH3:34])[N:29]=[CH:28][C:27]([C:35]#[N:36])=[C:26]2[NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([Br:44])[CH:39]=1>O1CCCC1>[Br:44][C:40]1[CH:39]=[C:38]([NH:37][C:26]2[C:25]3[C:30](=[CH:31][C:32]([O:33][CH3:34])=[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:35]#[N:36])[CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 685352-Butynoic acidHCID 98206456-Amino-4-[(3-bromophenyl)amino]-7-methoxy-quinoline-3-carbonitrile

Product 1

HCID 9803006N-[4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl]-2-butynamideYield 53.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.44 g (17.14 mmol) of 2-butynoic acid and 2.26 g (16.5 mmol) of isobutyl chloroformate in 30 ml of tetrahydrofuran at 0° C., with stirring , was added 3. 1 g (3.4 mmol) of N-methyl morpholine. This solution of the mixed anhydride was added to a stirred solution of 1.13 g (3.06 mmol) of 6-amino-4-[(3-bromophenyl)amino]-7-methoxy-3-quinolinecarbonitrile in 30 ml tetrahydrofuran in three portions over a 24 hour period. The solvent was removed. The residue was stirred with dilute sodium bicarbonate solution. Solid was collected and washed with water and ether. This was recrystallized from 1-butanol. The resulting solid was taken up in hot tetrahydrofuran and filtered through silica gel. The filtrate was concentrated and diluted with hexanes to give 0.71 g of N-[4-[(3-bromophenyl)amino]-3-cyano-7-methoxy -6-quinolinyl]-2-butynamide as a yellow powder: mass spectrum (electrospray, m/e): M+H 437.1,438.1.

Workup

  1. additionwas added 3
  2. customThe solvent was removed
  3. customSolid was collected
  4. washwashed with water and ether
  5. customThis was recrystallized from 1-butanol
  6. filtrationfiltered through silica gel
  7. concentrationThe filtrate was concentrated
  8. additiondiluted with hexanes

Sources & evidence

ORD record
ord-eea632789ecb40a9a926b4e9770ebbb0
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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