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

HRID 1935040Notes

Reaction equation

HRID 1935040 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.[NH2:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[N:37]=[CH:36][C:35]([C:41]#[N:42])=[C:34]2[NH:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([Br:50])[CH:45]=1>O1CCCC1.N1C=CC=CC=1>[Br:50][C:46]1[CH:45]=[C:44]([NH:43][C:34]2[C:33]3[C:38](=[CH:39][CH:40]=[C:31]([NH:30][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:32]=3)[N:37]=[CH:36][C:35]=2[C:41]#[N:42])[CH:49]=[CH:48][CH:47]=1

Participants

7

Reactant 4

HCID 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 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

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 tetrahydrofuran 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-72885d9aae7e4bf0b70858ab2312581e
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

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