Nitrogen → N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-diethylamino-2-butynamide

HRID 612123Notes

Reaction equation

HRID 612123 reaction equation
ClC(OCC(C)C)=O.[CH2:9]([N:11]([CH2:18][CH3:19])[CH2:12][C:13]#[C:14][C:15]([OH:17])=O)[CH3:10].CN1CCOCC1.N#N.[NH2:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[N:36]=[CH:35][C:34]([C:40]#[N:41])=[C:33]2[NH:42][C:43]1[CH:48]=[CH:47][CH:46]=[C:45]([Br:49])[CH:44]=1>N1C=CC=CC=1>[Br:49][C:45]1[CH:44]=[C:43]([NH:42][C:33]2[C:32]3[C:37](=[CH:38][CH:39]=[C:30]([NH:29][C:15](=[O:17])[C:14]#[C:13][CH2:12][N:11]([CH2:9][CH3:10])[CH2:18][CH3:19])[CH:31]=3)[N:36]=[CH:35][C:34]=2[C:40]#[N:41])[CH:48]=[CH:47][CH:46]=1

Participants

7

Reactant 5

HCID 947NitrogenHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 99677126-Amino-4-(3-bromophenylamino)quinoline-3-carbonitrileHCID 224666854-(Diethylamino)but-2-ynoic acid

Product 1

HCID 22466537N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-diethylamino-2-butynamideYield 28.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Isobutyl chloroformate (0.261 g, 1.91 mmol) was dropwise added into an ice cold solution of 4-diethylamino-2-butynoic acid (0.456 g, 2.94 mmol) and N-methylmorpholine (0.294 g, 2.94 mmol) in 50 mL of tetrahydrofuan under N2. After stirring for 30 min, a solution of 0.5 g (1.47 mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 3 mL of pyridine was added dropwise and the mixture was stirred at 0° C. for 2 hr. The reaction was quenched with ice water, poured into saturated sodium bicarbonate and brine, and extracted with ethyl acetate. The ethyl acetate layer was concentrated and purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate. The product was collected, and dried in vacuo to give 0.2 g (28.5%) of pale greenish yellow solid; ESMS m/z 476.2, 478.2 (M+H+); mp 133-135° C.

Workup

  1. stirringthe mixture was stirred at 0° C. for 2 hr
  2. customThe reaction was quenched with ice water
  3. additionpoured into saturated sodium bicarbonate and brine
  4. extractionextracted with ethyl acetate
  5. concentrationThe ethyl acetate layer was concentrated
  6. custompurified by thin-layer chromatography
  7. washeluted with 15% methanol in ethyl acetate
  8. customThe product was collected
  9. customdried in vacuo

Sources & evidence

ORD record
ord-6e482544bde54f41b2cbbe59ea3acdf9
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

Loading…