Hydrochloric Acid → HCID 67051623, compound

HRID 1809001Notes

Reaction equation

HRID 1809001 reaction equation
[F:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([CH2:16][NH:17]/[C:18](/SC)=[CH:19]/[N+:20]([O-:22])=[O:21])([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[NH4+:35].[ClH:36].O1CCOCC1>C(O)C.CO>[ClH:36].[NH2:35]/[C:18](/[NH:17][CH2:16][C:13]1([OH:15])[CH2:14][N:11]([C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[C:3]=2[NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[O:10])[CH2:12]1)=[CH:19]\[N+:20]([O-:22])=[O:21]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 312751,4-DioxaneHCID 67051949HCID 67051949, compound

Product 1

HCID 67051623HCID 67051623, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (0.05 g 0.08 mmol) 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(Z)-1-(methylthio)-2-nitroethenyl]amino}methyl)azetidin-3-ol in ethanol (2 mL) was added ammonium hydroxide (0.1 mL, 0.8 mmol) 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 (40 μL, 0.16 mmol) was added to the solution. A white precipitate formed and was collected by vacuum filtration. The solid was washed with hexane, and dried to afford 42 mg (87%) 3-({[(E)-1-amino-2-nitroethenyl]amino}methyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol hydrochloride. 1H NMR (400 MHz, d4-MeOH): 7.58 (t, 0.5H), 7.44 (t, 0.5H), 7.36 (m, 1H), 7.31 (m, 1H), 7.04 (m, 1H), 6.63 (m, 1H), 3.90-4.30 (m, 4H) 3.72 (s, 2H); MS (EI) for C19H17F3IN5O4: 564 (MH+).

Workup

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

Sources & evidence

ORD record
ord-15e1a2686f644499b02844a4c243a6d7
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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