Dicyclohexylcarbodiimide → N-[4-(3-Chloro-4-fluoroanilino)-3-cyano-7-(4-methyl-1-piperazinyl)-6-quinolinyl]-2-butynamide

HRID 379200Notes

Reaction equation

HRID 379200 reaction equation
[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].C1CCC(N=C=NC2CCCCC2)CC1.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[N:33]1[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]1)[N:29]=[CH:28][C:27]([C:40]#[N:41])=[C:26]2[NH:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[C:45]([Cl:50])[CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[Cl:50][C:45]1[CH:44]=[C:43]([CH:48]=[CH:47][C:46]=1[F:49])[NH:42][C:26]1[C:25]2[C:30](=[CH:31][C:32]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[C:23]([NH:22][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:24]=2)[N:29]=[CH:28][C:27]=1[C:40]#[N:41]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 11430Potassium CarbonateHCID 685352-Butynoic acidHCID 216972946-Amino-4-(3-chloro-4-fluroanilino)-7-(4-methyl-1-piperazinyl)-3-quinolinecarbonitrile

Product 1

HCID 21697308N-[4-(3-Chloro-4-fluoroanilino)-3-cyano-7-(4-methyl-1-piperazinyl)-6-quinolinyl]-2-butynamideYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-butynoic acid (0.25 g, 3.0 mmol) in 1.5 ml of DCM at 0° was added DCC (0.21 g, 1.0 mmol). After 15 m the mixture was warmed to 25°, recooled to 0°, and treated with 6-amino-4-(3-chloro-4-fluroanilino)-7-(4-methyl-1-piperazinyl)-3-quinolinecarbonitrile (0.21 g, 0.50 mmol) followed by 0.5 ml DCM rinse. The resulting mixture was stirred at 25° for 18 h and filtered to remove dicyclohexyl urea. The filtrate was partitioned with water which contained potassium carbonate (0.4 g, 3 mmol). The organic layer was washed with water, dried, and concentrated. The residue was passed as a solution in DCM onto a pad of silica gel. The product was eluted with 50:2:1 acetone-MeOH-TEA and concentrated to give 0.165 g amorphous solid; ms 477.2 (M+H)+, 239.1 (M+2H)+2.

Workup

  1. temperatureAfter 15 m the mixture was warmed to 25°
  2. customrecooled to 0°
  3. washrinse
  4. filtrationfiltered
  5. customto remove dicyclohexyl urea
  6. customThe filtrate was partitioned with water which
  7. washThe organic layer was washed with water
  8. customdried
  9. concentrationconcentrated
  10. washThe product was eluted with 50:2:1 acetone-MeOH-TEA
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c0d8376347fc496082ad3a5b95bfee91
Source dataset
uspto-grants-2001_10
Patent number
US06297258B1

Reaction notes

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