3-Chloropropionic acid → 3-Chloro-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-(4-morpholinyl)-6-quinolinyl]propanamide

HRID 379201Notes

Reaction equation

HRID 379201 reaction equation
[Cl:1][CH2:2][CH2:3][C:4]([OH:6])=O.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][O:36][CH2:35][CH2:34]1)[N:29]=[CH:28][C:27]([C:39]#[N:40])=[C:26]2[NH:41][C:42]1[CH:47]=[CH:46][C:45]([F:48])=[C:44]([Cl:49])[CH:43]=1>C(Cl)Cl>[Cl:1][CH2:2][CH2:3][C:4]([NH:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[N:33]1[CH2:34][CH2:35][O:36][CH2:37][CH2:38]1)[N:29]=[CH:28][C:27]([C:39]#[N:40])=[C:26]2[NH:41][C:42]1[CH:47]=[CH:46][C:45]([F:48])=[C:44]([Cl:49])[CH:43]=1)=[O:6]

Participants

5

Reactant 3

HCID 78993-Chloropropionic acidHCID 10868DicyclohexylcarbodiimideHCID 116898056-Amino-4-(3-chloro-4-fluroanilino)-7-(4-morpholinyl)-3-quinolinecarbonitrile

Product 1

HCID 216973173-Chloro-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-(4-morpholinyl)-6-quinolinyl]propanamideYield 77.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3-chloropropionic acid (0.65 g, 6.0 mmol)in 3 ml of DCM at 0° was added DCC (0.41 g, 2.0 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-morpholinyl)-3-quinolinecarbonitrile (0.40 g, 1.0 mmol) followed by 1 ml DCM rinse. The resulting mixture was stirred at 25° for 20 h, diluted with DCM, and stirred with aqueous sodium bicarbonate. The mixture was filtered to remove dicyclohexyl urea. The organic layer of the filtrate 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 25:25:2:1 DCM-EtOAc-MeOH-TEA and concentrated to give 0.38 g amorphous solid; ms 488.1(M+H)+.

Workup

  1. temperatureAfter 15 m the mixture was warmed to 25°
  2. customrecooled to 0°
  3. washrinse
  4. additiondiluted with DCM
  5. stirringstirred with aqueous sodium bicarbonate
  6. filtrationThe mixture was filtered
  7. customto remove dicyclohexyl urea
  8. washThe organic layer of the filtrate was washed with water
  9. customdried
  10. concentrationconcentrated
  11. washThe product was eluted with 25:25:2:1 DCM-EtOAc-MeOH-TEA
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-a29587f300db4dbc857e3c9d31367540
Source dataset
uspto-grants-2001_10
Patent number
US06297258B1

Reaction notes

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