Water → 3-fluorobenzyl 5-chloro-1-(3-fluorobenzyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

HRID 628359Notes

Reaction equation

HRID 628359 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11](O)=O)[NH:10][C:5]2=[CH:4][CH:3]=1.[C:14]([O-:17])([O-])=O.[Cs+].[Cs+].Br[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=1.[OH2:29]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]([O:17][CH2:14][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)=[O:29])[N:10]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)[C:5]2=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 680073-Fluorobenzyl bromideHCID 116655855-chloro-1H-pyrrolo(3,2-b)pyridine-2-carboxylic acid

Product 1

HCID 1181596253-fluorobenzyl 5-chloro-1-(3-fluorobenzyl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid (0.20 g, 1.0 mmol, from Example 99, Step 1) in DMF (4 mL) was treated with Cs2CO3 (1.3 g, 4.1 mmol, Aldrich) and after 10 minutes, α-bromo-3-fluorotoluene (0.25 mL, 2.0 mmol, Aldrich) was added. After stirring overnight, water was added and the product was extracted with three portions of EtOAc. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes afforded product as a white crystalline solid (0.40 g, 95%).

Workup

  1. extractionthe product was extracted with three portions of EtOAc
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washFlash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes afforded product as a white crystalline solid (0.40 g, 95%)

Sources & evidence

ORD record
ord-b76a1bd22efe4d48ad37d9cc770c4e1f
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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