Tetrahydrofuran → propane-1-sulfonic acid{2,4-difluoro-3-[5-(1H-pyrazolo[3,4-b]pyridin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide

HRID 60103Notes

Reaction equation

HRID 60103 reaction equation
[F:1][C:2]1[C:7]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16](B4OC(C)(C)C(C)(C)O4)[CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[C:6]([F:28])[CH:5]=[CH:4][C:3]=1[NH:29][S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31].Br[C:37]1[CH:38]=[C:39]2[CH:45]=[N:44][NH:43][C:40]2=[N:41][CH:42]=1.O1CCCC1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(#N)C>[F:1][C:2]1[C:7]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:37]4[CH:38]=[C:39]5[CH:45]=[N:44][NH:43][C:40]5=[N:41][CH:42]=4)[CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[C:6]([F:28])[CH:5]=[CH:4][C:3]=1[NH:29][S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 404274545-Bromopyrazolo[3,4-b]pyridineHCID 58368878propane-1-sulfonic acid (2,4-difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl)-amide

Product 1

HCID 53261843propane-1-sulfonic acid{2,4-difluoro-3-[5-(1H-pyrazolo[3,4-b]pyridin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
145 °C

Procedure

In a microwave vial, propane-1-sulfonic acid {2,4-difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide (30, 0.050 g, 0.099 mmol) is combined with 5-bromo-1H-pyrazolo[3,4-b]pyridine (31, 0.030 g, 0.15 mmol), 1 mL of tetrahydrofuran, 1 mL of acetonitrile, tetrakis(triphenylphosphine)palladium(0) (0.050 g, 0.043 mmol), and potassium carbonate (0.400 mL, 1.00 M in water). The reaction is heated at 145° C. for 45 minutes in a microwave, then extracted with ethyl acetate, and the organic layer is washed with water and brine. 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 methanol:dichloromethane. Appropriate fractions are combined, concentrated under vacuum and the resulting solid is further washed with a mixture of ethyl acetate:hexane to provide the desired compound. MS (ESI) [M−H+]−=495.05.

Workup

  1. extractionextracted with ethyl acetate
  2. washthe organic layer is washed with water and brine
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. customThe resulting material is purified by silica gel column chromatography
  7. washeluting with a gradient of methanol
  8. concentrationconcentrated under vacuum
  9. washthe resulting solid is further washed with a mixture of ethyl acetate

Sources & evidence

ORD record
ord-17713006c3a9419c86814b51a4b8649a
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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