Sodium Iodide → Tert-butyl 3-((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 1751066Notes

Reaction equation

HRID 1751066 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]2([CH2:46][CH2:45]2)[C:37]1=[O:47].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC.CO.ClCCl>[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:33][CH2:34][CH2:35][N:36]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[C:38]4([CH2:46][CH2:45]4)[C:37]3=[O:47])[CH2:8][CH2:7]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:20]=[C:21]([CH:29]=[CH:30][CH:31]=1)[C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23]

Participants

7

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 580467761'-(3-Chloropropyl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58046730Tert-butyl 3-((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 72%

Reagents, catalysts & solvents 2

HCID 6569Methyl Ethyl KetoneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

tert-Butyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate) (0.25 g, 0.593 mmol), 1′-(3-chloropropyl)spiro[cyclopropane-1,3′-indolin]-2′-one) (0.14 g, 0.593 mol), sodium iodide (0.027 g, 0.178 mmol), and potassium carbonate (0.12 g, 0.890 mmol) in 2-butanone (8 mL) were heated at 78° C. for 4 hours. The reaction was diluted with 10% methanol/dichloromethane, filtered, and evaporated. The residue was purified by PTLC (5% methanol/dichloromethane) to give product as a white solid (0.27 g, 72%); 1H NMR (DMSO-d6); δ1.51 (s, 9H); 1.53-1.63 (m, 6H); 1.80 (m, 2H); 2.37 (m, 2H); 2.51-2.63 (m, 2H); 2.63-2.76 (m, 4H); 3.82 (t, J=6.8 Hz, 2H); 4.58 (s, 2H); 4.61 (s, 2H); 6.76 (t, J=7.2 Hz, 1H); 6.85 (d, J=8.4 Hz, 2H); 6.98-7.00 (m, 2H); 7.19-7.24 (m, 4H); 7.49-7.56 (m, 2H); 7.79 (s, 1H); 7.82-7.84 9M, 1H); MS for C38H44N4O4 m/z 621 (M+H)+.

Workup

  1. filtrationfiltered
  2. customevaporated
  3. customThe residue was purified by PTLC (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-e3317502b90c4babb7a6e483dc078b13
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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