Dimethyl Sulfoxide → HCID 86621262, compound

HRID 605713Notes

Reaction equation

HRID 605713 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]1[C:13]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])=[C:14]([C:19]([N:21]2[CH2:24][C:23]([CH2:26][CH2:27][OH:28])([OH:25])[CH2:22]2)=[O:20])[CH:15]=[CH:16][C:17]=1[F:18].C(N(CC)CC)C>ClCCl>[F:11][C:12]1[C:13]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])=[C:14]([C:19]([N:21]2[CH2:24][C:23]([CH2:26][CH:27]=[O:28])([OH:25])[CH2:22]2)=[O:20])[CH:15]=[CH:16][C:17]=1[F:18]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 67051754HCID 67051754, compound

Product 1

HCID 86621262HCID 86621262, compoundYield 32.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of oxalyl chloride (13 μL, 0.15 mmol) in dichloromethane (1 mL) was cooled to −78° C., and DMSO (22 μL, 0.31 mmol) was then added. To this mixture was added 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(2-hydroxyethyl)azetidin-3-ol (67.8 mg, 0.14 mmol) as a suspension in dichloromethane (1 mL). After stirring at −78° C. for 10 min, triethylamine (78 μL, 0.56 mmol) was added and the mixture was allowed to warm to rt. The solution was diluted with dichloromethane, and washed with 0.5 N HCl. The aqueous phase wash then extracted with dichloromethane. The organic extracts were combined, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography to provide [1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]acetaldehyde as a white solid (22.1 mg, 0.045 mmol, 32% yield). 1H NMR (400 MHz, CDCl3): δ 9.82 (s, 1H), 8.46 (s, 1H), 7.39 (m, 1H), 7.33 (m, 1H), 7.11 (m, 1H), 6.81 (m, 1H), 6.61 (m, 1H), 4.32-3.96 (br m, 4H), 3.41 (t, 2H), 3.07 (s, 1H); MS (EI) for C18H14F3IN2O3: 491 (MH+).

Workup

  1. temperatureto warm to rt
  2. washwashed with 0.5 N HCl
  3. washThe aqueous phase wash
  4. extractionthen extracted with dichloromethane
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-661245d8470547199806d3676f2e3976
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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