Ethyl Acetate → methyl 3-((8-(3-(1H-indol-3-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 2362931Notes

Reaction equation

HRID 2362931 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].I[CH2:30][CH2:31][CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O>[NH:35]1[C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:33]([CH2:32][CH2:31][CH2:30][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]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 151749073-(3-iodopropyl)-1H-indoleHCID 66652852Methyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 66652188methyl 3-((8-(3-(1H-indol-3-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 46%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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 (871 mg, 2.11 mmol, 1.05 equiv), 3-(3-iodopropyl)-1H-indole (574 mg, 2.01 mmol, 1 equiv), and potassium carbonate (833 mg, 6.03 mmol, 3 equiv) in N—N-dimethylformamide was heated at 65° C. for 16 h. The reaction was cooled to ambient temperature and worked up using ethyl acetate and water. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using preparatory thin layer chromatography in 7% methanol in dichloromethane to afford the title compound as cream crystals (252 mg, 46%); 1H NMR (400 MHz, DMSO-d6): δ 1.62 (d, 2H, J=12 Hz), 1.84 (bs, 2H); 2.41 (bs, 2H); 2.57 (bs, 2H); 2.67 (bs, 2H); 2.71-2.75 (m, 4H); 3.85 (s, 3H); 4.59 (s, 2H); 4.63 (s, 2H); 6.77 (d, 1H, J=7.6 Hz); 6.85 (d, 2H, J=8 Hz); 6.96 (t, 1H, J=6.8 and 7.6 Hz); 7.03-7.07 (m, 1H); 7.13 (bs, 1H); 7.22 (t, 2H, J=8 Hz); 7.33 (d, 1H, J=8 Hz); 7.52-7.59 (m, 3H); 7.89-7.91 (m, 2H); 10.75 (s, 1H); MS for C33H36N4O3 m/z 537.06 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified

Sources & evidence

ORD record
ord-279a6249358e4a3680a40c81677f768b
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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