Water → 5-[Hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridine-2-carboxylic acid (4-chloro-phenyl)-amide

HRID 1367304

Reaction equation

HRID 1367304 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14](Br)=[CH:13][N:12]=2)=[O:10])=[CH:4][CH:3]=1.C([Li])(C)(C)C.[CH:23]([Si:26]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:40])[CH3:39])[N:27]1[C:31]2=[N:32][CH:33]=[CH:34][CH:35]=[C:30]2[C:29]([CH:36]=[O:37])=[CH:28]1)([CH3:25])[CH3:24].O>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH:36]([OH:37])[C:29]3[C:30]4[C:31](=[N:32][CH:33]=[CH:34][CH:35]=4)[N:27]([Si:26]([CH:38]([CH3:40])[CH3:39])([CH:41]([CH3:43])[CH3:42])[CH:23]([CH3:24])[CH3:25])[CH:28]=3)=[CH:13][N:12]=2)=[O:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 497589651H-Pyrrolo[2,3-B]pyridine-3-carboxaldehyde, 1-[tris(1-methylethyl)silyl]-HCID 595933715-Bromo-pyridine-2-carboxylic acid (4-chloro-phenyl)-amideHCID 178418306HCID 178418306, compound

Product 1

HCID 595933485-[Hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridine-2-carboxylic acid (4-chloro-phenyl)-amideYield 14.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To 5-Bromo-pyridine-2-carboxylic acid (4-chloro-phenyl)-amide (70, 0.50 g, 1.60 mmol) in tetrahydrofuran (20.0 mL), under an atmosphere of nitrogen at −78° C., tert-butyllithium (3.02 mL, 1.70 M in Hexane) was added. After 20 minutes, 1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (47, 0.39 g, 1.3 mmol, prepared as described in Example 18) in tetrahydrofuran (10.0 mL) was added to the reaction. The reaction was stirred at −78° C. for 1 hour, then allowed to warm to room temperature for 10 minutes. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% ethyl acetate in hexane to give the compound as colorless oil (71, 100 mg, 14%). MS (ESI) [M+H+]+=535.3.

Workup

  1. temperatureto warm to room temperature for 10 minutes
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d85ac2351082440a9b9d78f593a84847
Source dataset
uspto-grants-2011_02
Patent number
US07893075B2

Linked notes

Loading…