Sodium Iodide → tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 2363026Notes

Reaction equation

HRID 2363026 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=3)C(OC(C)(C)C)=O)[CH2:9]2)=[CH:4][CH:3]=1.Cl[CH2:34][CH2:35][CH2:36][N:37]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:48][CH2:47]2)[C:38]1=[O:49].[I-].[Na+].[C:52](=[O:55])([O-])[O-:53].[K+].[K+]>CC(=O)CC>[CH:46]1([N:39]2[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[N:37]([CH2:36][CH2:35][CH2:34][N:15]3[CH2:16][CH2:17][C:12]4([N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH2:9][N:10]([CH2:19][C:20]5[CH:21]=[CH:22][CH:30]=[CH:31][C:32]=5[C:52]([O:53][C:12]([CH3:17])([CH3:13])[CH3:11])=[O:55])[C:11]4=[O:18])[CH2:13][CH2:14]3)[C:38]2=[O:49])[CH2:48][CH2:47]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580467891-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-oneHCID 66652535Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 58046716tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 197.4%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
81 °C

Procedure

A mixture of tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (163.5 mg, 0.372 mmol, 1 equiv), 1-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-one (93 mg, 0.372 mmol, 1 equiv), sodium iodide (22.3 mg, 0.15 mmol, 0.4 equiv) and potassium carbonate (102.8 mg, 0.74 mmol, 2 equiv) in 2-butanone was stirred at 81° C. for 16 h. After cooling the reaction mixture, the crude mixture was partitioned between ethyl acetate and water. The organic layer was dried over MgSO4, filtered, concentrated, and the crude residue was purified using preparative thin layer chromatography to afford the title compound as a cream powder (240 mg, 65%); MS for C38H44FN5O4 m/z 654.34 (M+H)+.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customthe crude mixture was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe crude residue was purified

Sources & evidence

ORD record
ord-eeb73f4e7dc54ff5a8d8a4d7d72af75e
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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