Water → tert-Butyl 4-(2-(4-aminophenoxy)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

HRID 2361079Notes

Reaction equation

HRID 2361079 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:9]=[CH:10][C:3]=12.CC1(C)C(C)(C)OB([C:26]2[C:27]([O:32][C:33]3[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=3)=[N:28][CH:29]=[CH:30][CH:31]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.O.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[NH2:39][C:36]1[CH:37]=[CH:38][C:33]([O:32][C:27]2[C:26]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:9]=[CH:10][C:3]=34)=[CH:31][CH:30]=[CH:29][N:28]=2)=[CH:34][CH:35]=1

Participants

9

Reactant 6

HCID 962WaterHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 4060964Tri-t-butylphosphoniumHCID 247767911-Boc-4-chloro-7-azaindoleHCID 574164444-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)benzenamine

Product 1

HCID 57756226tert-Butyl 4-(2-(4-aminophenoxy)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

In an argon-purged sealed tube, tert-butyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (2.77 g, 11.0 mmol), 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)benzenamine (5.14 g, 16.5 mmol), sodium carbonate (3.49 g, 32.9 mmol), 1,4-dioxane (32.3 ml, 11.0 mmol), and water (11.7 ml, 11.0 mmol) were added. The tube was sealed, and the reaction was stirred at RT for 5 min. Palladium acetate (0.246 g, 1.10 mmol) and tri-t-butylphosphonium tetrafluororoborate (0.637 g, 2.19 mmol) were added, and the tube was sealed and heated to 100° C. After ˜105 min, heating was stopped, the reaction mixture was cooled to RT and passed through a pad of celite with an aid of EtOAc. The filtrate was dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography on 120 g silica gel column using DCM and 95:05 DCM:(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots, then 80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product. A viscous brown oil was obtained. After setting the oil at RT for several hours, crystals were formed. The oil was cooled to 0° C. and light yellow solid precipitated out after adding small amounts of hexanes and a little bit of ether in addition to scratching the wall of the flash with a spatula. The light yellow solid was filtered, washed with cold hexanes, and dried under vacuum. This solid, tert-butyl 4-(2-(4-aminophenoxy)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate was mainly the product according to 1H NMR. MS Calcd for C23H22N4O3: [M]+=402. Found: [M+H]+=403.

Workup

  1. customIn an argon-purged
  2. customsealed tube
  3. customThe tube was sealed
  4. customthe tube was sealed
  5. temperatureheated to 100° C
  6. waitAfter ˜105 min
  7. temperatureheating
  8. temperaturethe reaction mixture was cooled to RT
  9. dry with materialThe filtrate was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was purified by column chromatography on 120 g silica gel column
  13. custom(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots
  14. custom80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product
  15. customA viscous brown oil was obtained
  16. customat RT
  17. customfor several hours
  18. customcrystals were formed
  19. temperatureThe oil was cooled to 0° C.
  20. customlight yellow solid precipitated out
  21. additionafter adding small amounts of hexanes
  22. additiona little bit of ether in addition
  23. filtrationThe light yellow solid was filtered
  24. washwashed with cold hexanes
  25. customdried under vacuum

Sources & evidence

ORD record
ord-8d1b4e0e5e0c4b24baa708b9d8008ca0
Source dataset
uspto-grants-2014_04
Patent number
US08686155B2

Reaction notes

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