Iodine → (6S)-3-Iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2' (1'H)-one

HRID 2179445Notes

Reaction equation

HRID 2179445 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[C:8]2[CH2:23][C@@:13]3([C:21]4[C:16](=[N:17][CH:18]=[CH:19][CH:20]=4)[NH:15][C:14]3=[O:22])[CH2:12][C:9]2=[N:10][CH:11]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[I-:35].[K+].[OH-].[Na+].II.S([O-])([O-])(=O)=S.[Na+].[Na+]>O.C(#N)C>[I:35][C:6]1[CH:7]=[C:8]2[CH2:23][C@@:13]3([C:21]4[C:16](=[N:17][CH:18]=[CH:19][CH:20]=4)[NH:15][C:14]3=[O:22])[CH2:12][C:9]2=[N:10][CH:11]=1

Participants

10

Reactant 7

HCID 807IodineHCID 4875Potassium IodideHCID 6101p-Toluenesulfonic acidHCID 14798Sodium HydroxideHCID 24477Sodium ThiosulfateHCID 23668193Sodium NitriteHCID 58118676(S)-3-Amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Product 1

HCID 58118681(6S)-3-Iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2' (1'H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Procedure

A solution of sodium nitrite (36.1 g, 523 mmol) in water (20 mL) was added dropwise over 5 min to a solution of (6S)-3-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (prepared according to the procedures described in WO2008/020902, 66.0 g, 262 mmol) and p-toluenesulfonic acid (149 g, 785 mmol) in acetonitrile (650 mL) at 23° C. After stirring for 30 mitt, a solution of potassium iodide (109 g, 654 mmol) in water (20 mL) was then added over 5 minutes. The resulting mixture was stirred at 23° C. for 40 minutes, then diluted with water (1 L) and basified by the addition of solid NaOH (33.0 g, 824 mmol) with stirring. Iodine by-product was reduced by the addition of 10% aqueous sodium thiosulfate solution and stirring for an additional 30 minutes. The solids were collected by filtration, washed with water, and dried under nitrogen atmosphere to give the title compound, which was used without further purification. MS: m/z 363.9 (M+1).

Workup

  1. customprepared
  2. customat 23° C
  3. stirringThe resulting mixture was stirred at 23° C. for 40 minutes
  4. stirringwith stirring
  5. stirringstirring for an additional 30 minutes
  6. filtrationThe solids were collected by filtration
  7. washwashed with water
  8. customdried under nitrogen atmosphere

Sources & evidence

ORD record
ord-a25e99ada3914f19bb4f7d0bb86edb89
Source dataset
uspto-grants-2015_06
Patent number
US09067941B2

Reaction notes

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