Chloroacetyl chloride → N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-2-chloro-acetamide

HRID 732943Notes

Reaction equation

HRID 732943 reaction equation
[I:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=1)[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.C(N(CC)CC)C.[Cl:29][CH2:30][C:31](Cl)=[O:32]>C1COCC1>[NH2:15][C:9]1[C:8]([O:7][C:6]2[CH:16]=[C:2]([I:1])[C:3]([O:20][CH3:21])=[CH:4][C:5]=2[CH:17]([CH3:19])[CH3:18])=[CH:13][N:12]=[C:11]([NH:14][C:31](=[O:32])[CH2:30][Cl:29])[N:10]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 57839077N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-2-chloro-acetamideYield 61.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (3.6 g, 9 mmol) and 5.1 mL triethylamine was added to 120 mL dry THF, and the reaction mixture was cooled in an ice bath and stirred under nitrogen atmosphere. Chloroacetyl chloride (1.8 mL, 22.5 mmol) dissolved in 5 mL THF was added dropwise, and the reaction mixture was stirred for four hours, during which time the reaction mixture was allowed to slowly warm to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between water and methylene chloride. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting oil was purified by flash chromatography 0%-20% “Magic Base”/methylene chloride) to give 2.65 g of N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-2-chloro-acetamide as the major fraction.

Workup

  1. temperaturethe reaction mixture was cooled in an ice bath
  2. additionwas added dropwise
  3. stirringthe reaction mixture was stirred for four hours, during which time the reaction mixture
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customthe residue was partitioned between water and methylene chloride
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting oil was purified by flash chromatography 0%-20% “Magic Base”/methylene chloride)

Sources & evidence

ORD record
ord-5c069b5055f84910b992e2a780f9c5ec
Source dataset
uspto-grants-2009_09
Patent number
US07589090B2

Reaction notes

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