Sodium hydride → HCID 68561813, compound

HRID 459994Notes

Reaction equation

HRID 459994 reaction equation
[CH:1]([O:4][C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10]2)=[O:6])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:24][C:25]1[CH:29]=[C:28]([C:30]2[S:31][C:32]([Cl:35])=[CH:33][CH:34]=2)[O:27][N:26]=1>CN(C=O)C>[CH:1]([O:4][C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:24][C:25]1[CH:29]=[C:28]([C:30]3[S:31][C:32]([Cl:35])=[CH:33][CH:34]=3)[O:27][N:26]=1)[C:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10]2)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole2×HCID 68563348HCID 68563348, compound

Product 1

HCID 68561813HCID 68561813, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5.24 g 1H-Indole-2,5-dicarboxylic acid 2-ethyl ester 5-isopropyl ester in 80 ml DMF, 456 mg sodium hydride (60% in mineral oil) were added at RT. After stirring for 30 min 5.3 g 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, Christopher J.; 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 stirred for 2 h at RT. Then additional 91 mg sodium hydride (60% in mineral oil) and 1.06 g 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added and stirred for 2 h at RT. After removal of the solvent under reduced pressure the residue was taken-up in DCM (300 ml) and washed twice with water. The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel eluting with heptane/ethyl acetate 6:1. The fractions containing the product were collected and the solvent evaporated under reduced pressure. Yield: 6.3 g.

Workup

  1. customprepared
  2. stirringstirred for 2 h at RT
  3. customAfter removal of the solvent under reduced pressure the residue
  4. washwashed twice with water
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel eluting with heptane/ethyl acetate 6:1
  9. additionThe fractions containing the product
  10. customwere collected
  11. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-0bf4dc8c343c40ddbe7e3fbd589c96ef
Source dataset
uspto-grants-2007_03
Patent number
US07196103B2

Reaction notes

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