Sodium Iodide → Tert-butyl 3-((8-(3-(3,3-difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 2362967Notes

Reaction equation

HRID 2362967 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:20]=[C:21]([CH:29]=[CH:30][CH:31]=1)[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].Cl[CH2:33][CH2:34][CH2:35][N:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]([F:46])([F:45])[C:37]1=[O:47].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[F:46][C:38]1([F:45])[C:39]2[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:36]([CH2:35][CH2:34][CH2:33][N:9]2[CH2:10][CH2:11][C:6]3([N:5]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH2:4][N:3]([CH2:18][C:19]4[CH:20]=[C:21]([CH:29]=[CH:30][CH:31]=4)[C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[C:2]3=[O:1])[CH2:7][CH2:8]2)[C:37]1=[O:47]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580466161-(3-Chloropropyl)-3,3-difluoroindolin-2-oneHCID 58046667Tert-butyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 58046702Tert-butyl 3-((8-(3-(3,3-difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 46.9%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
81 °C

Procedure

A mixture of tert-butyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (300 mg, 0.71 mmol, 1 equiv), 1-(3-chloropropyl)-3,3-difluoroindolin-2-one (206.5 mg, 0.71 mmol, 1 equiv), sodium iodide (42.7 mg, 0.285 mmol, 0.4 equiv), and potassium carbonate (295.2 mg, 2.136 mmol, 3 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 preparatory thin layer chromatography in 5% methanol in dichloromethane to afford the title compound as cream crystals (210 mg, 46.8%); 1H NMR (400 MHz, DMSO-d6): δ 1.52 (s, 9H); 1.60 (d, 2H, J=13.2 Hz); 1.84 (t, 2H, J=6.8 and 6.4 Hz); 2.38 (t, 2H, J=6.4 Hz); 2.51 (bs, 2H); 2.71 (bs, 4H); 3.80 (t, 2H, J=6.8 Hz); 4.58 (s, 2H); 4.60 (s, 2H); 6.78 (t, 1H, J=7.2 Hz); 6.83 (d, 2H, J=8.4 Hz); 7.21-7.25 (m, 3H); 7.36 (d, 1H, J=8 Hz); 7.48-7.59 (m, 3H); 7.70 (d, 1H, J=6.8 Hz); 7.79 (s, 1H); 7.82-7.84 (m, 2H); MS for C36H40F2N4O4 m/z 631.11 (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-b7e9bca860774c4c9c29b10f403e52fa
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

Loading…