Potassium Iodide → 5-Morpholin-4-yl-pentanoic acid {4-[3-(4-tert-butyl-benzoyl)-thioureido]-phenyl}-amide

HRID 1889213Notes

Reaction equation

HRID 1889213 reaction equation
[C:1]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([NH:11][C:12](=[S:28])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25]Br)=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.[I-].[K+]>C(#N)C>[C:1]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([NH:11][C:12](=[S:28])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 8083MorpholineHCID 24772096HCID 24772096, compound

Product 1

HCID 247720985-Morpholin-4-yl-pentanoic acid {4-[3-(4-tert-butyl-benzoyl)-thioureido]-phenyl}-amide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-bromo-pentanoic acid {4-[3-(4-tert-butyl-benzoyl)-thioureido]-phenyl}-amide (intermediate JH140, prepared as described for tenovin 6) (80 mg, 0.16 mmol) in acetonitrile (4 mL) was added morpholine (0.4 mL) and potassium iodide (cat. amount). The reaction mixture was heated at reflux for 40 min, cooled to rt and concentrated in vacuo. The remaining residue was partitioned between 75% saturated aqueous sodium bicarbonate and CH2Cl2. The organic layer was dried with MgSO4 and concentrated in vacuo to give a crude beige solid. Purification by recrystallisation from EtOAc gave 5-morpholin-4-yl-pentanoic acid {4-[3-(4-tert-butyl-benzoyl)-thioureido]-phenyl}-amide which was converted to the hydrochloride salt by vapour diffusion. A solution of the dimethylamine in 25% CDCl3/diethyl ether was exposed to hydrogen chloride to give 1 as a white precipitate which was collected by filtration.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 40 min
  3. concentrationconcentrated in vacuo
  4. customThe remaining residue was partitioned between 75% saturated aqueous sodium bicarbonate and CH2Cl2
  5. dry with materialThe organic layer was dried with MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a crude beige solid
  8. customPurification
  9. customby recrystallisation from EtOAc

Sources & evidence

ORD record
ord-7fe4ea2ce5ba43f38e842f182888466f
Source dataset
uspto-grants-2013_08
Patent number
US08501991B2

Reaction notes

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