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

HRID 612124Notes

Reaction equation

HRID 612124 reaction equation
ClC(OCC(C)C)=O.[CH2:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]#[C:19][C:20]([OH:22])=O)[CH2:13][CH2:12]1)[CH3:10].CN1CCOCC1.N#N.[NH2:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[N:39]=[CH:38][C:37]([C:43]#[N:44])=[C:36]2[NH:45][C:46]1[CH:51]=[CH:50][CH:49]=[C:48]([Br:52])[CH:47]=1>N1C=CC=CC=1>[Br:52][C:48]1[CH:47]=[C:46]([NH:45][C:36]2[C:35]3[C:40](=[CH:41][CH:42]=[C:33]([NH:32][C:20](=[O:22])[C:19]#[C:18][CH2:17][N:14]4[CH2:13][CH2:12][N:11]([CH2:9][CH3:10])[CH2:16][CH2:15]4)[CH:34]=3)[N:39]=[CH:38][C:37]=2[C:43]#[N:44])[CH:51]=[CH:50][CH:49]=1

Participants

7

Reactant 5

HCID 947NitrogenHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 99677126-Amino-4-(3-bromophenylamino)quinoline-3-carbonitrileHCID 118056494-(N-ethylpiperazino)-2-butynoic acid

Product 1

HCID 53901162N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(N-ethylpiperazino)-2-butynamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Isobutyl chloroformate (0.785 g, 5.75 mmol) was dropwise added into an ice cold solution of 4-(N-ethylpiperazino)-2-butynoic acid (1.75 g, 8.85 mmol) and N-methylmorpholine (1.3453 g, 13.3 mmol) in 50 mL of tetrahydrofuan under N2. After stirring for 30 min, a solution of 1.5 g (4.42 mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 10 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 flash column chromatography. The product fractions were collected, and dried in vacuo to give 1.07 g (46%) of light brown solid; ESMS m/z 517.1, 519.1 (M+H+); mp 161° C. (dec).

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 flash column chromatography
  7. customThe product fractions were collected
  8. customdried in vacuo
  9. customto give 1.07 g (46%) of light brown solid

Sources & evidence

ORD record
ord-1fb9801efcc745e09aca6b40927828fc
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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