Sodium Iodide → tert-butyl 1-(3-(3-(3-(benzyloxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl)-1H-indole-2-carboxylate

HRID 1751053Notes

Reaction equation

HRID 1751053 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:32]=[CH:33][CH:34]=1)[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23].Cl[CH2:36][CH2:37][CH2:38][N:39]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=[C:40]1[C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH2:25]([O:24][C:22]([C:21]1[CH:20]=[C:19]([CH:34]=[CH:33][CH:32]=1)[CH2:18][N:3]1[C:2](=[O:1])[C:6]2([CH2:7][CH2:8][N:9]([CH2:36][CH2:37][CH2:38][N:39]3[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH:41]=[C:40]3[C:48]([O:50][C:51]([CH3:52])([CH3:54])[CH3:53])=[O:49])[CH2:10][CH2:11]2)[N:5]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:4]1)=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 58046631Benzyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateHCID 58046682tert-butyl 1-(3-chloropropyl)-1H-indole-2-carboxylate

Product 1

HCID 58046712tert-butyl 1-(3-(3-(3-(benzyloxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl)-1H-indole-2-carboxylateYield 19.6%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
81 °C

Procedure

A mixture of benzyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (807 mg, 1.65 mmol, 1 equiv), tert-butyl 1-(3-chloropropyl)-1H-indole-2-carboxylate (507 mg, 1.65 mmol, 1 equiv), sodium iodide (123.3 mg, 0.823 mmol, 0.5 equiv) and potassium carbonate (684.1 mg, 4.95 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 the Biotage flash chromatography system (SNAP 50 g cartridge, Rf=0.2, gradient—10%-50% ethyl acetate in hexanes) to afford the title compound as an oil (230 mg, 19%); MS for C44H48N4O5 m/z 713.37 (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-6fdef02e0d4840fe95d5480a6db11731
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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