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

HRID 628386Notes

Reaction equation

HRID 628386 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]([OH:13])=O)[NH:10][C:5]2=[CH:4][CH:3]=1.[C:14]([O-:17])([O-])=O.[Cs+].[Cs+].CS([O:24][CH2:25][C:26]1[CH:31]=[C:30]([Cl:32])[CH:29]=[C:28]([CH2:33][O:34][Si:35]([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:27]=1)(=O)=O>CN(C=O)C.O>[Si:35]([O:17][CH2:14][C:26]1[CH:27]=[C:28]([CH:29]=[C:30]([Cl:32])[CH:31]=1)[CH2:33][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:24][CH2:25][C:26]1[CH:31]=[C:30]([Cl:32])[CH:29]=[C:28]([CH2:33][O:34][Si:35]([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:27]=1)=[O:13])([C:48]([CH3:51])([CH3:49])[CH3:50])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 116655855-chloro-1H-pyrrolo(3,2-b)pyridine-2-carboxylic acid2×HCID 1235758393-({[Tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl methanesulfonate

Product 1

HCID 1237485193-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl 1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid (0.645 g, 3.28 mmol, from Example 99, Step 1) and Cs2CO3 (3.2 g, 9.8 mmol) were added to a solution of 3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl methanesulfonate (3.88 g, 7.93 mmol, from Step 3) in DMF (13 mL). Concurrently, a separate batch of 5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid (0.558 g, 2.81 mmol) was treated with the same reagents under the same conditions. After stirring each reaction overnight, the reactions were combined, diluted with water and extracted with three portions of EtOAc. 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 gradient from 0-50% EtOAc in hexanes. Yield: (3.11 g, 52%).

Workup

  1. customeach reaction overnight
  2. extractionextracted with three portions of EtOAc
  3. washThe combined organic extracts were washed sequentially with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by flash chromatography
  8. washeluting with a gradient from 0-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-29821709ec354481909fba7d7b8eb55e
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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