Sodium hydride → HCID 22394323, compound

HRID 1071680Notes

Reaction equation

HRID 1071680 reaction equation
C[O:2][C:3]([C:5]1[NH:6][C:7]2[C:12]([C:13]=1[I:14])=[C:11]([O:15][CH3:16])[CH:10]=[CH:9][C:8]=2[I:17])=[O:4].[H-].[Na+].Br[CH2:21][C:22]1[CH:26]=[C:25]([C:27]2[S:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[O:24][N:23]=1.BrCC1ON=C(C2SC(Cl)=CC=2)C=1>CN(C=O)C.O>[Cl:32][C:29]1[S:28][C:27]([C:25]2[O:24][N:23]=[C:22]([CH2:21][N:6]3[C:7]4[C:12](=[C:11]([O:15][CH3:16])[CH:10]=[CH:9][C:8]=4[I:17])[C:13]([I:14])=[C:5]3[C:3]([OH:2])=[O:4])[CH:26]=2)=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 223943745-Bromomethyl-3-(5-chloro-thiophen-2-yl)-isoxazoleHCID 68856424HCID 68856424, compound

Product 1

HCID 22394323HCID 22394323, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 200 mg 3,7-Diiodo-4-methoxy-1H-indole-2-carboxylic acid methyl ester in 2 ml DMF 20 mg (60% in oil) sodium hydride were added at RT. After stirring for 30 min 121 mg 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole [prepared by adopting a procedure described by Ewing, William R.; Becker, Michael R.; Choi-Sledeski, Yong Mi; Pauls, Heinz W.; He, Wei; Condon, Stephen M.; Davis, Roderick S.; Hanney, Barbara A.; Spada, Alfred P.; Burns, ChristopherJ.; Jiang, John Z.; Li, Aiwen; Myers, Michael R.; Lau, Wan F.; Poli, Gregory B; PCT Int. Appl. (2001), 460 pp. WO 0107436 A2] were added and the mixture was heated for 1 h at 60° C. After subsequent cooling of the reaction to RT and addition of 5 ml water the mixture was filtered through a chem elut® cartridge by elution with ethyl acetate. After concentration under reduced pressure the residue was treated with 30 mg lithium hydroxide monohydrate in THF/water 2:1. After stirring for 2 h at 60° C. the reaction was cooled to RT. The mixture was acidified with half concentrated hydrochloric acid to pH 2 and the precipitate collected by filtration and washed with 3 ml water The product was obtained as a white solid which was dried under reduced pressure. Yield: 200 mg.

Workup

  1. customprepared
  2. temperatureAfter subsequent cooling of the reaction to RT
  3. filtrationwas filtered through a chem elut® cartridge by elution with ethyl acetate
  4. concentrationAfter concentration under reduced pressure the residue
  5. additionwas treated with 30 mg lithium hydroxide monohydrate in THF/water 2:1
  6. temperaturewas cooled to RT
  7. filtrationthe precipitate collected by filtration
  8. washwashed with 3 ml water The product
  9. customwas obtained as a white solid which
  10. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-7284aaeb7337498e8d0ee00054efeffa
Source dataset
uspto-grants-2005_06
Patent number
US06906084B2

Reaction notes

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