Niclosamide → HCID 68760257, compound

HRID 1914488

Reaction equation

HRID 1914488 reaction equation
[CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([CH2:7][C:8]([OH:10])=[O:9])[C:4](=[O:11])[O:3]1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[Cl:24][C:25]1[CH:26]=[CH:27][C:28](O)=[C:29]([CH:43]=1)[C:30]([NH:32][C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][C:34]=1[Cl:42])=[O:31]>C(Cl)(Cl)Cl.N1C=CC=CC=1>[CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([CH2:7][C:8]([O:10][C:28]2[CH:27]=[CH:26][C:25]([Cl:24])=[CH:43][C:29]=2[C:30](=[O:31])[NH:32][C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][C:34]=2[Cl:42])=[O:9])[C:4](=[O:11])[O:3]1

Participants

7

Reactant 4

HCID 4477NiclosamideHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 108449602-((4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)acetic acid

Product 1

HCID 68760257HCID 68760257, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6212ChloroformSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of (R)-(−)-2,2-Dimethyl-5-oxo-1,3-dioxolane-4-acetic acid (Sigma-Aldrich, St. Louis, Mo.) (2.17 g, 12.46 mmol) in chloroform (24 mL) was treated with oxalyl chloride (2.11 mL, 25 mmol) and a drop of N,N-dimethylformamide was added. The progression of reaction was monitored by the observation of gas evolution by means of a bubbler. After 2 hours at room temperature, the reaction mixture was warmed to 50° C. for 2 hours, cooled to room temperature, and concentrated to remove volatiles. This residue was diluted with chloroform (10 mL) and added to a suspension of 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide (2.04 g, 6.23 mmol) in pyridine (30 mL) in which 4-dimethylaminopyride (20 mg) had been previously dissolved. The reaction mixture was stirred at room temperature for 16 h and then was partitioned between 1N aqueous HCl and ethyl acetate. The ethyl acetate solution was dried over magnesium sulfate and concentrated to a dark oil. The residue was dissolved in chloroform and placed upon a short column of silica gel (60 mm i.d.×15 mm). The product was eluted with chloroform and concentrated to an oil. The product was crystallized with a mixture of hexanes and ethyl acetate. 1HNMR (300 MHz, DMSO-d6): δ 1.456 (s, 3H), 1.495 (s, 3H), 4.939 (m, 1H), 7.352 (d, J=9 Hz, 1H, H3), 7.730 (dd, J=3.9 Hz, 1H, H4), 7.851 (d, J=3 Hz, 1H, H6), 8.110 (d, J=9 Hz, 1H, H6′), 8.255 (dd, J=3, 9 Hz, 1H, H5′), 8.411 (d, J=3 Hz, 1H, H3′), 10.481 (s, 1H, NH).

Workup

  1. customThe progression of reaction
  2. temperaturecooled to room temperature
  3. concentrationconcentrated
  4. customto remove volatiles
  5. additionThis residue was diluted with chloroform (10 mL)
  6. dissolutionhad been previously dissolved
  7. customwas partitioned between 1N aqueous HCl and ethyl acetate
  8. dry with materialThe ethyl acetate solution was dried over magnesium sulfate
  9. concentrationconcentrated to a dark oil
  10. dissolutionThe residue was dissolved in chloroform
  11. washThe product was eluted with chloroform
  12. concentrationconcentrated to an oil
  13. customThe product was crystallized with a mixture of hexanes and ethyl acetate

Sources & evidence

ORD record
ord-c5b4f695d6964a11bc18fa4d98a72df8
Source dataset
uspto-grants-2013_12
Patent number
US08614205B2

Linked notes

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