Potassium Hydroxide → propane-1-sulfonic acid (2,4-difluoro-3-{hydroxy-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-methyl}-phenyl)-amide

HRID 60101Notes

Reaction equation

HRID 60101 reaction equation
[CH3:1][C:2]1([CH3:18])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)[O:3]1.[OH-].[K+].[F:21][C:22]1[C:27]([CH:28]=[O:29])=[C:26]([F:30])[CH:25]=[CH:24][C:23]=1[NH:31][S:32]([CH2:35][CH2:36][CH3:37])(=[O:34])=[O:33]>CO>[F:21][C:22]1[C:27]([CH:28]([OH:29])[C:17]2[C:11]3[C:12](=[N:13][CH:14]=[C:9]([B:4]4[O:3][C:2]([CH3:18])([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5]4)[CH:10]=3)[NH:15][CH:16]=2)=[C:26]([F:30])[CH:25]=[CH:24][C:23]=1[NH:31][S:32]([CH2:35][CH2:36][CH3:37])(=[O:34])=[O:33]

Participants

5

Reactant 3

HCID 14797Potassium Hydroxide2×HCID 242087895-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 53419003N-(2,4-Difluoro-3-formylphenyl)-1-propanesulfonamide

Product 1

HCID 58368760propane-1-sulfonic acid (2,4-difluoro-3-{hydroxy-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-methyl}-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a round bottom flask, 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (27, 0.400 g, 1.64 mmol) is combined with 10 mL of methanol and potassium hydroxide (0.256 g, 4.56 mmol). Propane-1-sulfonic acid (2,4-difluoro-3-formyl-phenyl)-amide (28, 0.400 g, 1.52 mmol) is added and the reaction is stirred at room temperature for 3 hours, with additional potassium hydroxide added up to 7 equivalents. The reaction is concentrated under vacuum, the solid added to water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of 10-100% ethyl acetate (with 2.5% acetic acid) in hexanes. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound. MS (ESI) [M+H+]+=508.37.

Workup

  1. additionadded up to 7 equivalents
  2. concentrationThe reaction is concentrated under vacuum
  3. additionthe solid added to water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material is purified by silica gel column chromatography
  9. washeluting with a gradient of 10-100% ethyl acetate (with 2.5% acetic acid) in hexanes
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ad0b439bd1d94428b9d9edbfd0eedec6
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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