Chloroacetyl chloride → HCID 69060917, compound

HRID 2105133Notes

Reaction equation

HRID 2105133 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[NH:6]([C:13]1[N:18]=[C:17]([CH2:19][NH:20][CH2:21][CH2:22][OH:23])[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.[Br-].[Na+]>C(Cl)Cl>[NH:6]([C:13]1[N:18]=[C:17]([CH2:19][N:20]2[CH2:21][CH2:22][O:23][CH2:2][C:3]2=[O:4])[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 253881Sodium BromideHCID 69057135HCID 69057135, compound

Product 1

HCID 69060917HCID 69060917, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of chloroacetyl chloride (268 mg, 2.38 mmol) in dry DCM (5 ml) was added dropwise over 10 minutes to a stirred solution of 2-anilino-4-(2-hydroxyethylaminomethyl)pyrimidine (Method 19; 582 mg, 2.38 mmol) and triethylamine (332 μl, 2.38 mmol) in dry DCM (20 ml) under nitrogen. The reaction mixture was then stirred for 20 hours at ambient temperature. The mixture was diluted with DCM and washed with water (×2), saturated brine, dried (Na2SO4) and the volatiles removed by evaporation. The residue was dissolved in dry THF (20 ml), sodium bromide (227 mg, 2.2 mmol) added and the mixture stirred at 0° C. under nitrogen sodium hydride (88 mg of a 60% dispersion in oil) was added in one portion and the reaction stirred at 0° C. for 10 minutes and then at ambient temperature for 72 hours. The volatiles were removed by evaporation and the residue partition between EtOAc and water. The layers were separated and the organic layer washed with water, saturated brine, dried (Na2SO4) and the solvent removed by evaporation. The residue was purified by chromatography eluting with EtOAc. The purified product was triturated with diethyl ether, collected by filtration, washed with diethyl ether and dried to give the title compound (438 mg, 70%) as a white solid. NMR: 3.43 (t, 2H), 3.87 (t, 2H), 4.13 (s, 2H),4.52 (s, 2H), 6.72 (d, 1H), 6.93 (t, 1H), 7.25 (t 2H), 7.75 (d, 2H), 8.42 (d, 1H), 9.55 (s, 1H); m/z 285.

Workup

  1. washwashed with water (×2), saturated brine
  2. dry with materialdried (Na2SO4)
  3. customthe volatiles removed by evaporation
  4. dissolutionThe residue was dissolved in dry THF (20 ml)
  5. stirringthe mixture stirred at 0° C. under nitrogen sodium hydride (88 mg of a 60% dispersion in oil)
  6. additionwas added in one portion
  7. stirringthe reaction stirred at 0° C. for 10 minutes
  8. waitat ambient temperature for 72 hours
  9. customThe volatiles were removed by evaporation
  10. customthe residue partition between EtOAc and water
  11. customThe layers were separated
  12. washthe organic layer washed with water, saturated brine
  13. dry with materialdried (Na2SO4)
  14. customthe solvent removed by evaporation
  15. customThe residue was purified by chromatography
  16. washeluting with EtOAc
  17. customThe purified product was triturated with diethyl ether
  18. filtrationcollected by filtration
  19. washwashed with diethyl ether
  20. customdried

Sources & evidence

ORD record
ord-a7608893b5b54bc5889d76b42b64682b
Source dataset
uspto-grants-2009_08
Patent number
US07579344B2

Reaction notes

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