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

HRID 2363033Notes

Reaction equation

HRID 2363033 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:32]=[CH:31][CH:30]=[CH:29][C:21]=3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:9]2)=[CH:4][CH:3]=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:42][CH2:43][CH2:44][N:45]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]2([CH2:55][CH2:54]2)[C:46]1=[O:56]>CC(=O)CC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:13][CH2:14][N:15]([CH2:42][CH2:43][CH2:44][N:45]4[C:53]5[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=5)[C:47]5([CH2:55][CH2:54]5)[C:46]4=[O:56])[CH2:16][CH2:17]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:32]=[CH:31][CH:30]=[CH:29][C:21]=3[C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580467761'-(3-Chloropropyl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 66652103Tert-butyl 2-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 58046675Tert-butyl 2-((1-(4-fluorophenyl)-4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 44.2%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
78 °C

Procedure

To a solution of tert-butyl 2-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.2 g, 0.46 mmol), sodium iodide (0.021 g, 0.14 mmol) and potassium carbonate (0.095 g, 0.7 mmol) in 2-butanone (5 mL), was added 1′-(3-chloropropyl)spiro[cyclopropane-1,3′-indolin]-2′-one (0.107 g, 0.46 mmol). After stirring at 78° C. for 5 hours, the reaction mixture was filtered and isolated by Biotage flash chromatography (1-10% methanol/dichloromethane) and preparatory TLC (10% methanol/dichloromethane) to obtain the title compound (0.13 g, 44%); 1H NMR (DMSO-d6): δ 1.50 (t, 2H, J=6.4 Hz), 1.56-1.60 (m, 11H), 1.69 (d, 2H, J=9.2 Hz), 1.75 (t, 2H, J=6.4 Hz), 2.32-2.34 (m, 4H), 2.64-2.67 (m, 4H), 3.79 (t, 2H, J=6.4 Hz), 4.58 (s, 2H), 4.82 (s, 2H), 6.91-6.92 (m, 2H), 6.97-6.99 (m, 2H), 7.08-7.15 (m, 3H), 7.19 (d, 1H, J=6.8 Hz), 7.25-7.31 (m, 1H), 7.41 (t, 1H, J=8 Hz), 7.57 (t, 1H, J=7.6 Hz), 7.82 (dd, 1H, J=8 and 1.2 Hz); MS for C38H43FN4O4 m/z 639.4 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-ad622bd230b54d0cb31ea9500e80b814
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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