Water → N-{2,4-difluoro-3-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenyl}-3-methoxy-benzenesulfonamide

HRID 250576Notes

Reaction equation

HRID 250576 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)(=[O:12])=[O:11].C([N-]C(C)C)(C)C.[Li+].[CH:29]([Si:32]([CH:47]([CH3:49])[CH3:48])([CH:44]([CH3:46])[CH3:45])[N:33]1[C:37]2=[N:38][CH:39]=[CH:40][CH:41]=[C:36]2[C:35]([CH:42]=[O:43])=[CH:34]1)([CH3:31])[CH3:30].O>O1CCCC1>[F:1][C:2]1[C:7]([CH:42]([OH:43])[C:35]2[C:36]3[C:37](=[N:38][CH:39]=[CH:40][CH:41]=3)[N:33]([Si:32]([CH:44]([CH3:46])[CH3:45])([CH:47]([CH3:49])[CH3:48])[CH:29]([CH3:30])[CH3:31])[CH:34]=2)=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)(=[O:11])=[O:12]

Participants

6

Reactant 4

HCID 962WaterHCID 2724682Lithium diisopropylamideHCID 497589651H-Pyrrolo[2,3-B]pyridine-3-carboxaldehyde, 1-[tris(1-methylethyl)silyl]-HCID 58086624N-(2,4-difluorophenyl)-3-methoxybenzenesulfonamide

Product 1

HCID 58182210N-{2,4-difluoro-3-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenyl}-3-methoxy-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To N-(2,4-difluoro-phenyl)-3-methoxy-benzenesulfonamide (91, 0.148 g, 0.494 mmol) in tetrahydrofuran (10.0 mL) cooled in a −78° C. acetone/dry ice bath, under an atmosphere of nitrogen, was added lithium diisopropylamide (0.85 M in tetrahydrofuran, 1.45 mL, 1.23 mmol) dropwise. After 30 minutes, 1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (96, 0.15 g, 0.500 mmol, prepared as described in Example 12) was added in tetrahydrofuran (2.0 mL) into the reaction dropwise. Then the reaction was stirred for 1 hour at −78° C. and allowed to reach room temperature. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 40% ethyl acetate in hexane to give light yellow solid (92, 0.080 g, 26.8%). MS (ES1)[M+H+]+=602.

Workup

  1. customto reach room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 40% ethyl acetate in hexane
  9. customto give light yellow solid (92, 0.080 g, 26.8%)

Sources & evidence

ORD record
ord-9eb2dedc06914847ab29157300811bfd
Source dataset
uspto-grants-2011_01
Patent number
US07863288B2

Reaction notes

Loading…