Hydrochloric Acid → HCID 23289907, compound

HRID 366418Notes

Reaction equation

HRID 366418 reaction equation
C(OC([C:6]1[N:11]=[C:10]([CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:34])[C:21]([CH:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)([OH:28])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:15][CH2:14]2)[CH:9]=[CH:8][CH:7]=1)=O)C.[ClH:35].C1(P([N:50]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.Cl.O1CCOCC1>CO.[OH-].[Na+].C(O)(C)(C)C.C(N(CC)CC)C>[ClH:35].[ClH:35].[NH2:50][C:6]1[N:11]=[C:10]([CH2:12][N:13]2[CH2:14][CH2:15][CH:16]([NH:19][C:20](=[O:34])[C:21]([CH:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)([OH:28])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:17][CH2:18]2)[CH:9]=[CH:8][CH:7]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 199401P,P-Diphenylphosphinic azideHCID 204431481,4-Dioxane hydrochlorideHCID 23289912HCID 23289912, compound

Product 1

HCID 23289907HCID 23289907, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 6386tert-ButanolSolventHCID 8471TriethylamineSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 40 mg of N-[1-(6-ethoxycarbonyl-2-pyridylmethyl)piperidin-4-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide in 1 ml of methanol, 0.5 ml of 1N sodium hydroxide solution was added at room temperature, followed by 15 hours' stirring at the same temperature. The reaction mixture was made weakly acidic with 1N hydrochloric acid and concentrated under reduced pressure. The residue was dissolved in ethanol, and the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was purified by reverse phase ODS column chromatography (acetonitrile/water=2/1) to provide 27 mg of an oily substance. The product was dissolved in 1 ml of t-butanol. After addition of 20 mg of diphenylphosphoryl azide and 27 μl of triethylamine, the solution was refluxed for 18 hours. The solvent was distilled off, and the residue was purified by preparative thin layer chromatography [Kieselgel™ 60F254, Art 5744 (Merck), chloroform/methanol=10/1] to give 14 mg of an oily substance. The product was dissolved in 0.5 ml of methanol, and to which 4N hydrogen chloride/dioxane was added at room temperature, followed by an overnight stirring. The reaction mixture was solidified by drying under reduced pressure to give 13 mg of the title compound as a white solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in ethanol
  3. customthe insoluble matter was removed by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by reverse phase ODS column chromatography (acetonitrile/water=2/1)
  6. customto provide 27 mg of an oily substance
  7. temperaturethe solution was refluxed for 18 hours
  8. distillationThe solvent was distilled off
  9. customthe residue was purified by preparative thin layer chromatography [Kieselgel™ 60F254, Art 5744 (Merck), chloroform/methanol=10/1]
  10. customto give 14 mg of an oily substance
  11. waitfollowed by an overnight
  12. stirringstirring
  13. customby drying under reduced pressure

Sources & evidence

ORD record
ord-16675c2841564584a3b0a501e0e7dbee
Source dataset
uspto-grants-2000_10
Patent number
US06130232

Reaction notes

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