Sodium Thiosulfate → HCID 86621263, compound

HRID 1672913Notes

Reaction equation

HRID 1672913 reaction equation
[F:1][C:2]1[C:3]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([C:16]([CH3:20])([CH3:19])[CH2:17][OH:18])([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>ClCCl>[F:1][C:2]1[C:3]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[C:4]([C:9]([N:11]2[CH2:12][C:13]([C:16]([CH3:20])([CH3:19])[CH:17]=[O:18])([OH:15])[CH2:14]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 16223021HCID 16223021, compound

Product 1

HCID 86621263HCID 86621263, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(2-hydroxy-1,1-dimethylethyl)azetidin-3-ol (200 mg, 0.38 mmol) and Dess-Martin periodinane (240 mg, 0.57 mmol) in dichloromethane (2 mL) was stirred at room temperature for 2 hours. 10% aqueous sodium thiosulfate (2 mL), and saturated aqueous sodium bicarbonate (2 mL) was added and the mixture was stirred at room temperature for 15 minute. The mixture was partitioned and the aqueous layer was extracted twice using dichloromethane. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo, to afford a white solid which was purified by column chromatography. Eluting with 30% ethyl acetate in hexanes, the isolated product was concentrated in vacuo to afford 100 mg, 0.20 mmol (53%) of 2-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-methylpropanal as a white solid, which was immediately dissolved in tetrahydrofuran (2 mL). To the solution was added isopropylamine (34 μL, 0.40 mmol), followed by triacetoxyborohydride (212 mg, 1.0 mmol). The solution was stirred at room temperature for 15 hours. The reaction mixture was concentrated in vacuo and partitioned between 20% aqueous citric acid and ethyl acetate. The aqueous portion was extracted twice using ethyl acetate, and the combined organic portion was washed with saturated aqueous sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by preparative reverse phase HPLC. The isolated product was concentrated in vacuo to afford 50 mg, 0.07 mmol (36%) of 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{1,1-dimethyl-2-[(1-methylethyl)amino]ethyl}azetidin-3-ol acetate salt as a white solid. 1H NMR (400 MHz, DMSO): 8.47 (br s, 1H), 7.55 (d, 1H), 7.36-7.29 (m, 2H), 7.22-7.15 (m, 1H), 6.68-6.63 (m, 1H), 4.17-4.08 (m, 2H), 3.76-3.73 (m, 1H), 3.56-3.52 (m, 1H), 2.58-2.51 (m, 1H), 2.45-2.37 (m, 2H), 0.92 (t, 6H), 0.78 (d, 6H); MS (EI) for C23H27F3IN3O2: 562 (MH+).

Workup

  1. stirringthe mixture was stirred at room temperature for 15 minute
  2. customThe mixture was partitioned
  3. extractionthe aqueous layer was extracted twice using dichloromethane
  4. washThe combined organic portion was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a white solid which
  9. customwas purified by column chromatography
  10. washEluting with 30% ethyl acetate in hexanes
  11. concentrationthe isolated product was concentrated in vacuo

Sources & evidence

ORD record
ord-e292839b40464f549122ff69191d5dca
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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