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

HRID 588976Notes

Reaction equation

HRID 588976 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 min, a solution of potassium iodide (109 g, 654 mmol) in water (20 mL) was added over 5 min. The resulting mixture was stirred at 23° C. for 40 min, 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 min. 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 min
  4. stirringwith stirring
  5. stirringstirring for an additional 30 min
  6. filtrationThe solids were collected by filtration
  7. washwashed with water
  8. customdried under nitrogen atmosphere

Sources & evidence

ORD record
ord-b91879266b25440387906763a97227d9
Source dataset
uspto-grants-2016_01
Patent number
US09227973B2

Reaction notes

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