Hydrochloric Acid → HCID 178479331, compound

HRID 1672931Notes

Reaction equation

HRID 1672931 reaction equation
[F:1][C:2]1[C:16]([F:17])=[CH:15][CH:14]=[C:13]([C:18]([N:20]2[CH2:25][C:22]3([O:24][CH2:23]3)[CH2:21]2)=[O:19])[C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:6]=1[F:12].[N+:26]([NH:29][C:30]([NH2:32])=[NH:31])([O-:28])=[O:27].[OH-].[Na+].[ClH:35].O1CCOCC1>O1CCCC1.CO>[ClH:35].[F:1][C:2]1[C:3]([NH:4][C:5]2[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:6]=2[F:12])=[C:13]([C:18]([N:20]2[CH2:21][C:22]([CH2:23][NH:32][C:30]([NH:29][N+:26]([O-:28])=[O:27])=[NH:31])([OH:24])[CH2:25]2)=[O:19])[CH:14]=[CH:15][C:16]=1[F:17]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 86287517NitroguanidineHCID 86621266HCID 86621266, compound

Product 1

HCID 178479331HCID 178479331, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 2,3-difluoro-N-(2-fluoro-4-iodophenyl)-6-(1-oxa-5-azaspiro[2,3]hex-5-ylcarbonyl)aniline (0.15 g, 0.33 mmol), prepared using procedures similar to those described in Example 21, and nitroguanidine (0.1 g, 1.00 mmol) in tetrahydrofuran (3.00 mL) an aqueous solution of sodium hydroxide (1.0 mL, 2.0 mmol) was added and the reaction mixture was stirred at 70° C. for 16 hours. The reaction mixture was concentrated in vacuo. The crude product was purified by reverse phase preparative HPLC. The fractions were collected, and the solvent was concentrated. The residue was partitioned with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, brine and dried over anhydrous sodium sulfate. Filtration and concentration resulted in an amorphous residue, which was dissolved in methanol, and 4 N HCl in dioxane (80 μL, 0.33 mmol) was added to the solution. A white precipitate formed and was collected by filtration. The solid was washed with hexane, and dried to afford 76 mg (38%) 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]methyl}-3-nitroguanidine hydrochloride. 1H NMR (400 MHz, d4-MeOH): 7.46 (2d, 1H), 7.36 (m, 1H), 7.29 (m, 1H), 7.02 (m, 1H), 6.63 (m, 1H), 4.22 (m, 1H), 4.01 (m, 2H), 3.86 (m, 1H), 3.51 (d, 2H); MS (EI) for C18H16F3IN6O4: 565 (MH+).

Workup

  1. customprepared
  2. additionwas added
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customThe crude product was purified by reverse phase preparative HPLC
  5. customThe fractions were collected
  6. concentrationthe solvent was concentrated
  7. customThe residue was partitioned with ethyl acetate
  8. washThe organic layer was washed with saturated aqueous sodium bicarbonate, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationFiltration and concentration
  11. customresulted in an amorphous residue, which
  12. customA white precipitate formed
  13. filtrationwas collected by filtration
  14. washThe solid was washed with hexane
  15. customdried

Sources & evidence

ORD record
ord-71833c4799f948238557632f371d52c7
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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