Sodium Iodide → tert-butyl 3-((8-(3-(3-(3-methoxy-3-oxopropyl)-1H-indol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 2362990Notes

Reaction equation

HRID 2362990 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]([CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48])=[CH:37]1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH3:50][O:49][C:47](=[O:48])[CH2:46][CH2:45][C:38]1[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)[CH:37]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 58046667Tert-butyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateHCID 58046806methyl 3-(1-(3-chloropropyl)-1H-indol-3-yl)propanoate

Product 1

HCID 58046653tert-butyl 3-((8-(3-(3-(3-methoxy-3-oxopropyl)-1H-indol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 56.1%

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 (500 mg, 1.186 mmol, 1 equiv) and methyl 3-(1-(3-chloropropyl)-1H-indol-3-yl)propanoate (384.4 mg, 1.186 mmol, 1 equiv), sodium iodide (88.88 mg, 0.593 mmol, 0.5 equiv) and potassium carbonate (492 mg, 3.56 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 preparative thin layer chromatography in 5% methanol in dichloromethane to afford the title compound as a white solid (442 mg, 56%); 1H NMR (400 MHz, DMSO-d6): δ 1.52 (s, 9H); 1.63 (d, 2H, J=12 Hz); 1.90-1.96 (m, 2H); 2.24 (bs, 2H); 2.61-2.70 (m, 8H); 2.96 (t, 2H, J=7.6 Hz); 3.57 (s, 3H); 4.20 (t, 2H, J=6.4 and 6.8 Hz); 4.59 (s, 2H); 4.61 (s, 2H); 6.77 (t, 1H, J=7.2 and 7.6 Hz); 6.87 (d, 2H, J=8.4 Hz); 6.99 (t, 1H, J=7.6 Hz); 7.10 (t, 1H, J=7.6 and 6.8 Hz); 7.17 (s, 1H); 7.24 (t, 2H, J=7.2 and 8.4 Hz); 7.46-7.53 (m, 4H); 7.79-7.84 (m, 2H); MS for C40H48N4O5 m/z 665 (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-e2a74bacb99f4b519c5272a1578e0993
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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