Hydrochloric Acid → HCID 68527051, compound

HRID 884183Notes

Reaction equation

HRID 884183 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:38]=[CH:39][C:40]=1[Cl:41])[C:5]([N:7](C(=O)C1C=CC(Cl)=C(Cl)C=1)[C:8]1[CH:9]=[CH:10][C:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23](OCC)=[O:24])=[CH:17][CH:16]=2)=[N:12][CH:13]=1)=[O:6].[OH-].[Na+].Cl.[CH2:45]([N:55]1[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1)[C:46]1[CH:54]=[CH:53][C:52]2[O:51][CH2:50][O:49][C:48]=2[CH:47]=1.C(N(CC)CC)C.C(P(=O)(OCC)OCC)#N>C1COCC1.C(O)C.O>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:38]=[CH:39][C:40]=1[Cl:41])[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23]([N:58]3[CH2:59][CH2:60][N:55]([CH2:45][C:46]4[CH:54]=[CH:53][C:52]5[O:51][CH2:50][O:49][C:48]=5[CH:47]=4)[CH2:56][CH2:57]3)=[O:24])=[CH:17][CH:16]=2)=[N:12][CH:13]=1)=[O:6]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 76257Diethyl cyanophosphonateHCID 944261-PiperonylpiperazineHCID 68525915HCID 68525915, compound

Product 1

HCID 68527051HCID 68527051, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-(4-{5-[bis(3,4-dichlorobenzoyl)amino]-2-pyridylmethyl}phenyl)propionate (177 mg, 0.281 mmol) in THF (5 mL) and ethanol (5 mL) were added 5 M aqueous sodium hydroxide (0.0929 mL, 0.463 mmol) and water (1 mL), and the resulting solution was refluxed for 1 hour. To this reaction solution was added 5 M hydrochloric acid (0.12 mL), and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was dissolved in DMF (3 mL), and to the resulting solution were then added 1-piperonylpiperazine (102 mg, 0.463 mmol), triethylamine (0.137 mL, 0.983 mmol) and diethyl cyanophosphonate (0.0703 mL, 463 mmol), and stirred for 1.5 hours at room temperature. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=70:1→40:1→20:1), to thereby yield 44.1 mg of a free form. This free form was dissolved in ethanol (5 mL) and 5 M hydrochloric acid (0.03 mL) by heating. The solvent was then evaporated, and the obtained solid was recrystallized from water-containing isopropanol, to thereby yield 19.6 mg of the title compound.

Workup

  1. temperaturethe resulting solution was refluxed for 1 hour
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated
  6. dissolutionThe residue was dissolved in DMF (3 mL)
  7. extractionextracted with ethyl acetate
  8. washThe ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customevaporated
  11. customThe residue was purified by silica gel column chromatography (dichloromethane:methanol=70:1→40:1→20:1)
  12. dissolutionThis free form was dissolved in ethanol (5 mL)
  13. temperature5 M hydrochloric acid (0.03 mL) by heating
  14. customThe solvent was then evaporated
  15. customthe obtained solid was recrystallized from water-
  16. additioncontaining isopropanol

Sources & evidence

ORD record
ord-a9771058177843b0b8380183074fd32c
Source dataset
uspto-grants-2012_08
Patent number
US08236826B2

Reaction notes

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