Cesium carbonate → 3-({[tert-Butyl(diphenyl)silyl]oxy}methyl)benzyl 1-[3-({[tert-butyl(diphenyl)sily]oxy}methyl)benzyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

HRID 628379Notes

Reaction equation

HRID 628379 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]([OH:13])=[O:12])[NH:10][C:5]2=[CH:4][CH:3]=1.[C:14]([O-:17])([O-])=O.[Cs+].[Cs+].[C:20]([Si:24]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45]Cl)[CH:40]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C>[Si:24]([O:17][CH2:14][C:43]1[CH:44]=[C:39]([CH:40]=[CH:41][CH:42]=1)[CH2:38][N:10]1[C:5]2[C:6](=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:8]=[C:9]1[C:11]([O:13][CH2:45][C:41]1[CH:42]=[CH:43][CH:44]=[C:39]([CH2:38][O:37][Si:24]([C:20]([CH3:23])([CH3:21])[CH3:22])([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:40]=1)=[O:12])([C:20]([CH3:23])([CH3:21])[CH3:22])([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 116655855-chloro-1H-pyrrolo(3,2-b)pyridine-2-carboxylic acidHCID 220737533-(t-Butyldiphenylsiloxymethy)benzyl chloride

Product 1

HCID 1317353483-({[tert-Butyl(diphenyl)silyl]oxy}methyl)benzyl 1-[3-({[tert-butyl(diphenyl)sily]oxy}methyl)benzyl]-5-chloro-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 (0.803 g, 4.08 mmol, from Example 99, Step 1) in DMF (20 mL) was treated with Cs2CO3 (4.0 g, 12 mmol), followed by the addition of tert-butyl{[3-(chloromethyl)benzyl]oxy}diphenylsilane (3.9 g, 9.9 mmol, from Step 2). After stirring overnight, the crude reaction mixture was partitioned between water and ethyl acetate and the aqueous layer was extracted with an additional two portions of ethyl acetate. The combined organic extracts were washed sequentially with water and brine, dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a slow gradient from 0-20% EtOAc/hexanes. Yield: (2.18 g, 58%).

Workup

  1. customthe crude reaction mixture
  2. customwas partitioned between water and ethyl acetate
  3. extractionthe aqueous layer was extracted with an additional two portions of ethyl acetate
  4. washThe combined organic extracts were washed sequentially with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by flash chromatography
  9. washeluting with a slow gradient from 0-20% EtOAc/hexanes

Sources & evidence

ORD record
ord-87aa8eef9ae5487bbd858bfde371c224
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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