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

HRID 1751108Notes

Reaction equation

HRID 1751108 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:21]=[C:22]([CH:30]=[CH:31][CH:32]=3)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:9]2)=[CH:4][CH:3]=1.[I-].[Na+].C(=O)(O)[O-].[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]([F:54])([CH3:53])[C:45]1=[O:55]>CC(=O)CC>[F:54][C:46]1([CH3:53])[C:47]2[C:52](=[CH:51][CH:50]=[CH:49][CH:48]=2)[N:44]([CH2:43][CH2:42][CH2:41][N:15]2[CH2:14][CH2:13][C:12]3([N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH2:9][N:10]([CH2:19][C:20]4[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=4)[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[C:11]3=[O:18])[CH2:17][CH2:16]2)[C:45]1=[O:55]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 516893Potassium BicarbonateHCID 666525311-(3-Chloropropyl)-3-fluoro-3-methylindolin-2-oneHCID 66652535Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 58046812Tert-butyl 3-((8-(3-(3-fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 91%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
78 °C

Procedure

To a solution of tert-butyl 3-((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 bicarbonate (0.095 g, 0.69 mmol) in 2-butanone (5 mL), was added 1-(3-chloropropyl)-3-fluoro-3-methylindolin-2-one (0.11 g, 0.46 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 (0.27 g, 91%); 1H NMR (DMSO-d6): δ 1.52 (s, 9H), 1.65-1.71 (m, 5H), 1.77 (t, 2H, J=6.8 Hz), 2.32-2.34 (m, 4H), 2.66-2.68 (m, 4H), 3.72 (t, 2H, J=6.8 Hz), 4.57 (d, 4H, J=15.6 Hz), 6.88-6.91 (m, 2H), 7.07-7.13 (m, 3H), 7.18 (d, 1H, J=8 Hz), 7.39 (t, 1H, J=8 Hz), 7.47-7.56 (m, 3H), 7.78 (s, 1H), 7.82 (dt, 1H, J=6.8 and 2 Hz); MS for C37H42F2N4O4 m/z 645.5 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-baab139afb934c9d867cf643d7a8fc2b
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

Loading…