Oxalyl chloride → (E)-N-{4-[4-(benzyloxy)-3-chloroanilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide

HRID 748617Notes

Reaction equation

HRID 748617 reaction equation
C(Cl)(=O)C(Cl)=O.Cl.[CH3:8][N:9]([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13](O)=[O:14].[NH2:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH2:29][CH3:30])[N:24]=[CH:23][C:22]([C:31]#[N:32])=[C:21]2[NH:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[C:36]([Cl:48])[CH:35]=1.C(=O)(O)[O-].[Na+]>C(#N)C.CN1CCCC1=O.CN(C)C=O>[CH2:41]([O:40][C:37]1[CH:38]=[CH:39][C:34]([NH:33][C:21]2[C:20]3[C:25](=[CH:26][C:27]([O:28][CH2:29][CH3:30])=[C:18]([NH:17][C:13](=[O:14])/[CH:12]=[CH:11]/[CH2:10][N:9]([CH3:16])[CH3:8])[CH:19]=3)[N:24]=[CH:23][C:22]=2[C:31]#[N:32])=[CH:35][C:36]=1[Cl:48])[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 114081766-Amino-4-[4-(benzyloxy)-3-chloroanilino]-7-ethoxy-3-quinolinecarbonitrileHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochloride

Product 1

HCID 11353443(E)-N-{4-[4-(benzyloxy)-3-chloroanilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamideYield 53.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A 1.74 ml (2.54 g, 0.02 moles) portion of oxalyl chloride was added to 3.31 grams (0.02 moles) of (E)-4-(dimethylamino)-2-butenoic acid hydrochloride in 75 ml of acetonitrile. To this was added a small drop of dimethylformamide. The reaction was heated and stirred in an oil bath at 63° for 20 minutes, giving an orange solution. This solution as concentrated in vacuo without the application of heat to about half its original volume. This solution was cooled in an ice bath and a solution of 4.45 g (0.01 moles) of the 6-amino-4-[4-(benzyloxy)-3-chloroanilino]-7-ethoxy-3-quinolinecarbonitrile in 50 ml of N-methylpyrrolidone was added in a stream. The reaction was cooled and stirred for 2 hours. The reaction was poured onto 100 ml of saturated aqueous sodium bicarbonate in ice. On standing the resulting gum solidified and the solid was filtered. This solid was chromatographed on silica gel. The column was washed with 3 liters of 1:19 methanol-ethyl acetate, then the product was eluted with 3 liters of 1:5:94 triethylamine-methanol-ethyl acetate. Concentration of the eluate gave a solid, which was filtered to give 2.96 grams of the title compound. From the filtrate was obtained an additional 1.0 grams of product. Total: 3.96 g.

Workup

  1. temperatureThe reaction was heated
  2. customgiving an orange solution
  3. concentrationThis solution as concentrated in vacuo without the application
  4. temperatureof heat to about half its original volume
  5. temperatureThis solution was cooled in an ice bath
  6. temperatureThe reaction was cooled
  7. stirringstirred for 2 hours
  8. filtrationthe solid was filtered
  9. customThis solid was chromatographed on silica gel
  10. washThe column was washed with 3 liters of 1:19 methanol-ethyl acetate
  11. washthe product was eluted with 3 liters of 1:5:94 triethylamine-methanol-ethyl acetate
  12. customConcentration of the eluate gave a solid, which
  13. filtrationwas filtered

Sources & evidence

ORD record
ord-ed6e97b183804520a38a909a8d511177
Source dataset
uspto-grants-2008_07
Patent number
US07399865B2

Reaction notes

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