Valeryl chloride → 3-(4-{2-[3-(2,4-difluorophenyl)-1-pentylureido]ethoxy}phenyl)-2-ethoxypropionic Acid

HRID 1744462Notes

Reaction equation

HRID 1744462 reaction equation
C([O:3][C:4](=[O:20])[CH:5]([O:17][CH2:18][CH3:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][NH2:16])=[CH:9][CH:8]=1)C.[C:21](Cl)(=O)[CH2:22][CH2:23][CH2:24][CH3:25].FC1C(F)=C(F)C(F)=C2C(=O)OC(=O)C=12.[F:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[N:51]=[C:52]=[O:53]>C(Cl)Cl.N1C=CC=CC=1>[F:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[NH:51][C:52](=[O:53])[N:16]([CH2:15][CH2:14][O:13][C:10]1[CH:9]=[CH:8][C:7]([CH2:6][CH:5]([O:17][CH2:18][CH3:19])[C:4]([OH:3])=[O:20])=[CH:12][CH:11]=1)[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]

Participants

7

Reactant 4

HCID 61186Valeryl chlorideHCID 69545Tetrafluorophthalic anhydrideHCID 5932582,4-Difluorophenyl isocyanateHCID 108589313-[4-(2-Aminoethoxy)phenyl]-2-ethoxypropionic acid ethyl ester

Product 1

HCID 222303673-(4-{2-[3-(2,4-difluorophenyl)-1-pentylureido]ethoxy}phenyl)-2-ethoxypropionic Acid

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of the compound obtained in Example 1, Step c (42 mg) in methylene chloride (2 ml) was added with pyridine (32 μl) and valeryl chloride (21.4 μl, Tokyo Kasei Kogyo) and stirred at room temperature for 4 hours. The reaction mixture was added with tetrafluorophthalic anhydride (22 mg) and further stirred for 2 hours. The reaction mixture was added with a polyamine resin (100 mg, prepared by the same method as described in Example 3), stirred for 1.5 hours and filtered, and the filtrate was concentrated. The resulting residue was dissolved in THF (1 ml), added with ethyl acetate (200 μl) and borane/dimethyl sulfide complex (36 μl, Tokyo Kasei Kogyo) and stirred at room temperature for 20 hours. The reaction mixture was added with ethanol (0.2 ml) and stirred at room temperature for 1 hour and at 50° C. for 1 hour. The reaction mixture was concentrated, and the resulting residue was dissolved in methylene chloride, washed with 1 N aqueous sodium hydroxide, dried and concentrated. Because a TLC analysis verified that the reaction was incomplete, a THF solution of the residue was prepared again and subjected to the reduction reaction and the post-treatments again. By using the resulting compound, the title compound (5.6 mg) was obtained in the same manner as that of Example 3 except that 2,4-difluorophenyl isocyanate (Aldrich) was used instead of the 2,4-dimethoxyphenyl isocyanate.

Workup

  1. stirringfurther stirred for 2 hours
  2. customprepared by the same method
  3. stirringstirred for 1.5 hours
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe resulting residue was dissolved in THF (1 ml)
  7. additionadded with ethyl acetate (200 μl) and borane/dimethyl sulfide complex (36 μl, Tokyo Kasei Kogyo)
  8. stirringstirred at room temperature for 20 hours
  9. additionThe reaction mixture was added with ethanol (0.2 ml)
  10. stirringstirred at room temperature for 1 hour and at 50° C. for 1 hour
  11. concentrationThe reaction mixture was concentrated
  12. dissolutionthe resulting residue was dissolved in methylene chloride
  13. washwashed with 1 N aqueous sodium hydroxide
  14. customdried
  15. concentrationconcentrated
  16. customa THF solution of the residue was prepared again
  17. customsubjected to the reduction reaction

Sources & evidence

ORD record
ord-2b879d45c2194024b7bc69bda9065095
Source dataset
uspto-grants-2006_03
Patent number
US07015345B2

Reaction notes

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