Sodium Iodide → 6-Bromo-4-{5-[(2,2-dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole

HRID 38834Notes

Reaction equation

HRID 38834 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25]Cl)=[N:23][N:24]=2)[CH:3]=1.[CH3:27][C:28]1([CH3:34])[O:33][CH2:32][CH2:31][NH:30][CH2:29]1.CCN(C(C)C)C(C)C.[I-].[Na+]>C(#N)C.C(Cl)Cl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:30]3[CH2:31][CH2:32][O:33][C:28]([CH3:34])([CH3:27])[CH2:29]3)=[N:23][N:24]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 189596742,2-Dimethylmorpholine2×HCID 666956686-bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 666956776-Bromo-4-{5-[(2,2-dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazoleYield 91.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of 6-bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole (200 mg, 0.441 mmol) in acetonitrile (2 ml) was added 2,2-dimethylmorpholine (102 mg, 0.882 mmol, available from Chembridge Corporation) and the mixture heated at 70° C. for 18 hr. The mixture was cooled to room temperature and a further portion of 2,2-dimethylmorpholine (102 mg, 0.882 mmol), DIPEA (0.154 mL, 0.882 mmol) and sodium iodide (66.1 mg, 0.441 mmol) were added. The mixture was then heated again at 70° C. for 2 hours. The mixture was cooled to room temperature, diluted with DCM and washed with water. The organic layer was separated through a hydrophobic frit and the solvent removed in vacuo. The resulting yellow oil was dried in a vacuum oven at 60° C. overnight to give a pale yellow solid, which was dissolved in DCM (10 ml) and washed with dilute HCl (10 ml) followed by water (10 ml), separating the layers using a hydrophobic frit. The DCM was removed in vacuo to give the title compound as a cream solid (214 mg).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. temperatureThe mixture was then heated again at 70° C. for 2 hours
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with water
  5. customThe organic layer was separated through a hydrophobic frit
  6. customthe solvent removed in vacuo
  7. customThe resulting yellow oil was dried in a vacuum oven at 60° C. overnight
  8. customto give a pale yellow solid, which
  9. washwashed with dilute HCl (10 ml)
  10. customseparating the layers
  11. customThe DCM was removed in vacuo

Sources & evidence

ORD record
ord-112e9482f57345c49da6371b6ddbc7ff
Source dataset
uspto-grants-2013_09
Patent number
US08524751B2

Reaction notes

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