Oxalyl chloride → 4-[(3-Bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazoline

HRID 1069011Notes

Reaction equation

HRID 1069011 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][CH2:8]/[CH:9]=[CH:10]/[C:11]([OH:13])=O.[Br:14][C:15]1[CH:16]=[C:17]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([NH2:32])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:18]=[CH:19][CH:20]=1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O.O1CCCC1.O.C(OCC)(=O)C>[Br:14][C:15]1[CH:16]=[C:17]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([NH:32][C:11](=[O:13])[CH:10]=[CH:9][CH2:8][Br:7])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:18]=[CH:19][CH:20]=1

Participants

10

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamineHCID 64364114-Bromocrotonic acid

Product 1

HCID 544131234-[(3-Bromophenyl)amino]-6-[(4-bromo-1-oxo-2-buten-1-yl)amino]-quinazolineYield 84.7%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 2.88 mL (4.19 g; 0.033 mole) portion of oxalyl chloride was added to 2.47 g (0.015 moles) of 4-bromo crotonic acid suspended in 25 mL of dichloromethane. To this was added 3 drops of N,N-dimethylformamide. After stirring for about 1 ½ hours, the solvents were removed in vacuo, and the residual oil was dissolved in 20 mL of tetrahydrofuran. This solution was cooled in an ice bath, and a solution of 4.72 g (0.015 moles) of N-(3-bromophenyl)-4,6-quinazolindiamine in 50 mL of tetrahydrofuran was added dropwise. This was followed, still with cooling by the dropwise addition of 2.61 mL (1.99g; 0.015 moles) of diisopropylethylamine in 10 mL of tetrahydrofuran. After cooling and stirring an hour, 80 mL of ethyl acetate and 100 mL of water were added. The layers were separated, and the aqueous layer was extracted with 100 mL of 1:1 tetrahydrofuran ethyl acetate. The combined organic layers were washed with 50 mL of brine, then dried over sodium sulfate. The solution was taken to a solid in vacuo. This solid was digested for an hour with 100 mL of ethyl acetate to give 5.87 g (84%) of product. Mass spectrum (m/e) M+H 460.8, 62.8, 464.8.

Workup

  1. customthe solvents were removed in vacuo
  2. dissolutionthe residual oil was dissolved in 20 mL of tetrahydrofuran
  3. temperatureThis solution was cooled in an ice bath
  4. temperatureAfter cooling
  5. stirringstirring an hour
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with 100 mL of 1:1 tetrahydrofuran ethyl acetate
  8. washThe combined organic layers were washed with 50 mL of brine
  9. dry with materialdried over sodium sulfate
  10. waitThis solid was digested for an hour with 100 mL of ethyl acetate

Sources & evidence

ORD record
ord-dc937c4353bc45ac856f06c5d18c7843
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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