Butanoic acid, 4-chloro-4-oxo-, methyl ester → Methyl 3-(5-(5-iodo-2-isopropyl-4-methoxyphenoxy)-4-aminopyrimidin-2-ylcarbamoyl)propanoate

HRID 1714855Notes

Reaction equation

HRID 1714855 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.Cl[C:23](=[O:30])[CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27]>ClCCl.N1C=CC=CC=1>[CH3:29][O:28][C:26](=[O:27])[CH2:25][CH2:24][C:23]([NH:14][C:11]1[N:10]=[C:9]([NH2:15])[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]=1)=[O:30]

Participants

5

Reactant 2

HCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 68510970Methyl 3-(5-(5-iodo-2-isopropyl-4-methoxyphenoxy)-4-aminopyrimidin-2-ylcarbamoyl)propanoate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (0.56 g, 1.4 mmoles) in dichloromethane (40 ml) and pyridine (4 ml) was slowly added methyl 4-chloro-4-oxobutyrate (1.3 ml, 7.5 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, dissolved in a mixture of concentrated aqueous ammonium hydroxide and methanol (10 ml/40 ml), and stirred at room temperature for one hour. Solvent was evaporated 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 (1% methanol in dichloromethane) to give crude N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-succinamic acid methyl ester (0.54 g, not shown) as a foam, MS (M+H)=515.

Workup

  1. customsolvent was removed under reduced pressure
  2. washThe residue was washed twice with water
  3. dissolutiondissolved in a mixture of concentrated aqueous ammonium hydroxide and methanol (10 ml/40 ml)
  4. stirringstirred at room temperature for one hour
  5. customSolvent was evaporated under reduced pressure
  6. customthe residue was partitioned between dichloromethane and water
  7. washThe organic phase was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography (1% methanol in dichloromethane)

Sources & evidence

ORD record
ord-06a84fd579ac46349494d7b3250433c1
Source dataset
uspto-grants-2010_09
Patent number
US07799796B2

Reaction notes

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