Potassium Carbonate → Methyl 3-((8-(4-(4-fluorophenyl)-4-oxobutyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 2362921Notes

Reaction equation

HRID 2362921 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:26]=[CH:27][CH:28]=1)[C:22]([O:24][CH3:25])=[O:23].[F:29][C:30]1[CH:35]=[CH:34][C:33]([C:36](=[O:41])[CH2:37][CH2:38][CH2:39]I)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:29][C:30]1[CH:31]=[CH:32][C:33]([C:36](=[O:41])[CH2:37][CH2:38][CH2:39][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:26]=[CH:27][CH:28]=4)[C:22]([O:24][CH3:25])=[O:23])[C:2]3=[O:1])[CH2:7][CH2:8]2)=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 30162324'-Fluoro-4-iodobutyrophenoneHCID 66652852Methyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 66652364Methyl 3-((8-(4-(4-fluorophenyl)-4-oxobutyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (500 mg, 1.2 mmol, 1 equiv), 1-(4-fluorophenyl)-4-iodobutan-1-one (351.1 mg, 1.2 mmol, 1 equiv), and potassium carbonate (497.6 mg, 3.6 mmol, 3 equiv) in N,N-dimethylformamide was heated at 65° C. for 16 h. The reaction was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic layer was dried over MgSO4, and concentrated in vacuo. The crude was purified using preparatory thin layer chromatography in 10% methanol in dichloromethane followed by a purification using preparatory high performance liquid chromatography to afford the acetate salt of the title compound as a yellow powder (65 mg, ˜10%); 1H NMR (400 MHz, DMSO-d6): δ 1.58 (d, 2H, J=14 Hz), 1.81-1.88 (m, 2H); 2.39-2.47 (m, 4H); 2.67-2.75 (m, 4H); 3.04 (t, 2H, J=6.4 and 7.2 Hz); 3.84 (s, 3H); 4.57 (s, 2H); 4.61 (s, 2H); 6.74-6.77 (m, 3H); 7.14-7.18 (m, 2H); 7.32-7.37 (m, 2H); 7.52-7.58 (m, 2H); 7.88-7.90 (m, 2H); 8.05-8.08 (m, 2H); 10.82 (s, 1H); MS for C32H34FN3O4 m/z 544.02 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude was purified
  6. customfollowed by a purification

Sources & evidence

ORD record
ord-146669c97f064b63805480ce856b7dc1
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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