Diethylamine → 4-Diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide

HRID 1069013Notes

Reaction equation

HRID 1069013 reaction equation
[CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].[Br:6][C:7]1[CH:8]=[C:9]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([NH:24][C:25](=[O:30])[CH:26]=[CH:27][CH2:28]Br)[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH:10]=[CH:11][CH:12]=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C=O>[Br:6][C:7]1[CH:8]=[C:9]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([NH:24][C:25](=[O:30])[CH:26]=[CH:27][CH2:28][N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 8021DiethylamineHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 544131234-[(3-Bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazoline

Product 1

HCID 541919604-Diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amideYield 59.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5.17 mL (3.65 g; 50 mmoles) of diethylamine in 20 mL of tetrahydrofuran was stirred and cooled in an ice bath, and a solution of 1.16 g (2.5 mmoles) of 4-Bromo-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide in 10 mL of tetrahydrofuran and 5 mL of N,N-dimethylformamide was added dropwise. After stirring for 2 hours, 45 mL of ethyl acetate and 30 mL of saturated aqueous sodium bicarbonate were added, and the layers were separated. The organic layer was extracted with 25 mL of brine, dried over sodium sulfate, and taken to an oil in vacuo. This was chromatographed on silica gel with 1:9 methanol methylene chloride to give 677 mg (59%) of the desired product, which melted at 196-199° C. Mass spectrum (m/e) M+2H 228.5.

Workup

  1. temperaturecooled in an ice bath
  2. customthe layers were separated
  3. extractionThe organic layer was extracted with 25 mL of brine
  4. dry with materialdried over sodium sulfate
  5. customThis was chromatographed on silica gel with 1:9 methanol methylene chloride

Sources & evidence

ORD record
ord-4d294ca3ae3c454287e077f347b3f392
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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