Ethanol → HCID 86627653, compound

HRID 599414Notes

Reaction equation

HRID 599414 reaction equation
O=C1C2[C:5](=CC=CC=2)[C:4](=O)[N:3]1[O:12][CH2:13][C:14]1[N:15]([CH2:28][CH2:29][CH2:30][CH2:31][NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:16]2[C:21]([CH3:22])=[C:20]([CH3:23])[N:19]3[N:24]=[N:25][N:26]=[C:18]3[C:17]=2[N:27]=1.O.NN.[CH2:40](O)C>>[CH3:23][C:20]1[N:19]2[N:24]=[N:25][N:26]=[C:18]2[C:17]2[N:27]=[C:14]([CH2:13][O:12][N:3]=[C:4]([CH3:5])[CH3:40])[N:15]([CH2:28][CH2:29][CH2:30][CH2:31][NH:32][S:33]([CH3:36])(=[O:34])=[O:35])[C:16]=2[C:21]=1[CH3:22]

Participants

4

Reactant 3

HCID 702EthanolHCID 24654Hydrazine hydrate (1:1)HCID 67052465HCID 67052465, compound

Product 1

HCID 86627653HCID 86627653, compound

Procedure

A mixture of N-[4-(8-{[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]methyl}-5,6-dimethyl-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridin-7-yl)butyl]methanesulfonamide (205 mg, 0.40 mmol), hydrazine hydrate (0.4 mL), and ethanol (4 mL) was stirred for 30 minutes. The solvent was removed under reduced pressure and the residue was partitioned between 1 M aqueous HCl (20 mL) and dichloromethane (10 mL). The aqueous phase was washed with dichloromethane (3×8 mL), then was adjusted to pH 12 with 1 M aqueous sodium hydroxide and was concentrated under reduced pressure. To the residue was added acetone (10 mL) and methanol (10 mL), and the reaction mixture was stirred for 3 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane (20 mL) and saturated aqueous sodium carbonate (20 mL). The aqueous phase was extracted with dichloromethane (3×10 mL). The organic layers were combined, washed with saturated aqueous sodium carbonate (3×10 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 20-40% CMA in chloroform, where CMA is 80:18:2 chloroform/methanol/concentrated ammonium hydroxide) to yield 91 mg of N-{4-[5,6-dimethyl-8-({[(1-methylethylidene)amino]oxy}methyl)-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridin-7-yl]butyl}methanesulfonamide as a white foam.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between 1 M aqueous HCl (20 mL) and dichloromethane (10 mL)
  3. washThe aqueous phase was washed with dichloromethane (3×8 mL)
  4. concentrationwas concentrated under reduced pressure
  5. additionTo the residue was added acetone (10 mL) and methanol (10 mL)
  6. stirringthe reaction mixture was stirred for 3 hours
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was partitioned between dichloromethane (20 mL) and saturated aqueous sodium carbonate (20 mL)
  9. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  10. washwashed with saturated aqueous sodium carbonate (3×10 mL)
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 20-40% CMA in chloroform, where CMA is 80:18:2 chloroform/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-c69237703526407292596a5e316775b5
Source dataset
uspto-grants-2011_03
Patent number
US07897767B2

Reaction notes

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