Valeryl chloride → HCID 58826021, compound

HRID 1714854Notes

Reaction equation

HRID 1714854 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:22](Cl)(=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26]>ClCCl.N1C=CC=CC=1>[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]([NH:15][C:6](=[O:7])[CH2:5][CH2:4][CH2:3][CH3:2])=[N:10][C:11]([NH:14][C:22](=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26])=[N:12][CH:13]=1

Participants

5

Reactant 2

HCID 61186Valeryl chlorideHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 58826021HCID 58826021, compoundYield 19.8%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a 0° C. solution of 5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (1.0 g, 2.5 mmoles) in dichloromethane (80 ml) and pyridine (3 ml), was slowly added valeryl chloride (2.4 ml, 20.2 mmoles). The mixture was stirred at room temperature for 60 hours, and then solvent was removed under reduced pressure. The residue was washed twice with water and then dissolved in dichloromethane. This organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was passed through a silica gel plug (40% ethyl acetate in hexane). The crude mixture was dissolved in a mixture of concentrated ammonium hydroxide aqueous solution and methanol (3 ml/27 ml) and stirred at room temperature for 15 minutes. Solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography (20%, 35% ethyl acetate in hexane), to give crude pentanoic acid [5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-2-pentanoylamino-pyrimidin-4-yl]-amide was obtained, which was crystallized from ether and hexane to give pure pentanoic acid [5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-2-pentanoylamino-pyrimidin-4-yl]-amide (141 mg) as white solid, MS (M+H)=569. The filtrate from the recrystallization was dried and re-dissolved in a mixture of concentrated ammonium hydroxide aqueous solution and methanol (10 ml/40 ml) and stirred at room temperature for 5 hours. This solution was concentrated under reduced pressure, and the residue was partitioned between dichloromethane and water. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (30% ethyl acetate in hexanes), and recrystallized from ethyl acetate and hexane to give pure pentanoic acid [4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-amide (395 mg) as white solid, MS (M+H)=485.

Workup

  1. customTo a 0° C.
  2. customsolvent was removed under reduced pressure
  3. washThe residue was washed twice with water
  4. dissolutiondissolved in dichloromethane
  5. dry with materialThis organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe crude mixture was dissolved in a mixture of concentrated ammonium hydroxide aqueous solution and methanol (3 ml/27 ml)
  9. stirringstirred at room temperature for 15 minutes
  10. customSolvent was removed under reduced pressure
  11. customthe residue was purified by silica gel chromatography (20%, 35% ethyl acetate in hexane)
  12. customto give crude pentanoic acid [5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-2-pentanoylamino-pyrimidin-4-yl]-amide
  13. customwas obtained
  14. customwhich was crystallized from ether and hexane

Sources & evidence

ORD record
ord-be2e8c2439aa428d810f3cefbde3c637
Source dataset
uspto-grants-2010_09
Patent number
US07799796B2

Reaction notes

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