Diisopropylethylamine → 4-[(3-Bromophenyl)amino]-6-[(4-{N-[(ethoxycarbonyl)methyl]-N-methylamino}-1-oxo-2-buten-1-yl)-amino]-quinazoline

HRID 488417Notes

Reaction equation

HRID 488417 reaction equation
CCN(C(C)C)C(C)C.Cl.[CH2:11]([O:13][C:14](=[O:18])[CH2:15][NH:16][CH3:17])[CH3:12].[Br:19][C:20]1[CH:21]=[C:22]([NH:26][C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[C:34]([NH:37][C:38](=[O:43])[CH:39]=[CH:40][CH2:41]Br)[CH:35]=3)[N:30]=[CH:29][N:28]=2)[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.C(OCC)(=O)C>[Br:19][C:20]1[CH:21]=[C:22]([NH:26][C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[C:34]([NH:37][C:38](=[O:43])[CH:39]=[CH:40][CH2:41][N:16]([CH2:15][C:14]([O:13][CH2:11][CH3:12])=[O:18])[CH3:17])[CH:35]=3)[N:30]=[CH:29][N:28]=2)[CH:23]=[CH:24][CH:25]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 516892Sodium BicarbonateHCID 544131234-[(3-Bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazoline

Product 1

HCID 542024624-[(3-Bromophenyl)amino]-6-[(4-{N-[(ethoxycarbonyl)methyl]-N-methylamino}-1-oxo-2-buten-1-yl)-amino]-quinazoline

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

13.94 ml of Hünig base are pipetted into a suspension of 9.37 g of sarcosine ethylester hydrochloride in 25 ml of tetrahydrofuran while cooling with an ice bath. Then a solution of 2.00 g of 4-[(3-bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazoline in 10 ml of dimethylformamide is added dropwise within 15 minutes. The reaction mixture is allowed to come up to ambient temperature overnight in an ice bath. For working up, 25 ml of saturated sodium hydrogen carbonate solution and 50 ml of ethyl acetate are added. The organic phase is separated off and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The dark-brown oily residue is stirred with 50 ml of water, the precipitate formed is suction filtered and washed with water. The crude product is purified by chromatography on a silica gel column with methylene chloride/methanol (50:1 to 20:1). Yield: 1.00 g (46% of theory), Melting point: 182-183° C. Mass spectrum (ESI*): m/z=496, 498 [M−H]*

Workup

  1. temperaturewhile cooling with an ice bath
  2. customThe organic phase is separated off
  3. extractionthe aqueous phase is extracted with ethyl acetate
  4. washThe combined organic phases are washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated by evaporation
  7. customthe precipitate formed
  8. filtrationfiltered
  9. washwashed with water
  10. customThe crude product is purified by chromatography on a silica gel column with methylene chloride/methanol (50:1 to 20:1)

Sources & evidence

ORD record
ord-18efe5c82e2b41278e39fc6f275ea503
Source dataset
uspto-grants-2005_12
Patent number
US06972288B1

Reaction notes

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