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

HRID 1751077Notes

Reaction equation

HRID 1751077 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:31]=[CH:30][CH:29]=[CH:28][C:20]=1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:41][CH2:42][CH2:43][N:44]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[C:46]2([CH2:54][CH2:53]2)[C:45]1=[O:55]>CC(=O)CC>[O:1]=[C:2]1[C:6]2([CH2:7][CH2:8][N:9]([CH2:41][CH2:42][CH2:43][N:44]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[C:46]4([CH2:54][CH2:53]4)[C:45]3=[O:55])[CH2:10][CH2:11]2)[N:5]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:31]=[CH:30][CH:29]=[CH:28][C:20]=1[C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580467761'-(3-Chloropropyl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 66652177Tert-butyl 2-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 58046740Tert-butyl 2-((4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 62%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
78 °C

Procedure

To a solution of tert-butyl 2-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.2 g, 0.47 mmol), sodium iodide (0.021 g, 0.14 mmol) and potassium carbonate (0.097 g, 0.7 mmol) in 2-butanone (5 mL), was added 1′-(3-chloropropyl)spiro[cyclopropane-1,3′-indolin]-2′-one (0.112 g, 0.47 mmol). After stirring at 78° C. for 2 hours, the reaction mixture was filtered and isolated by Biotage flash chromatography (1-10% methanol/dichloromethane) to obtain the title compound (0.18 g, 62%); 1H NMR (DMSO-d6): δ 1.51 (t, 4H, J=7.2 Hz), 1.57 (s, 9H), 1.67 (d, 2H, J=12.4 Hz), 1.79 (t, 2H, J=6.8 Hz), 2.36 (t, 2H, J=6.8 Hz), 2.54-2.74 (m, 6H), 3.81 (t, 2H, J=7.2 Hz), 4.62 (s, 2H), 4.84 (s, 2H), 6.76 (t, 1H, J=7.2 Hz), 6.84 (d, 2H, J=8 Hz), 6.96-7.02 (m, 2H), 7.17-7.27 (m, 5H), 7.41 (t, 1H, J=6.8 Hz), 7.57 (t, 1H, J=7.6 Hz), 7.83 (dd, 1H, J=8 and 1.2 Hz); MS for C38H44N4O4 m/z 621.12 (M+H)+.

Workup

  1. filtrationthe reaction mixture was filtered
  2. customisolated by Biotage flash chromatography (1-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-003d5430f1d94514b883d98a674f2542
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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