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

HRID 227772Notes

Reaction equation

HRID 227772 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+].C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCOCC1>[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

8

Reactant 4

HCID 10340Sodium CarbonateHCID 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 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

In an argon-purged sealed tube, tert-butyl 4-chloro-1-H-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), water (11.7 mL) were added. The reaction was stirred at rt for 5 min. Then palladium acetate (0.246 g, 1.10 mmol) and tri-t-butylphosphonium tetrafluroroborate (0.637 g, 2.19 mmol) were added. The tube was sealed and heated to 100° C. After 1 h 45 min, the reaction was monitored and found to be complete. The reaction mixture was cooled to rt and passed through a pad of celite, washing with 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, small amounts of crystaline colonies 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)-1-H-pyrrolo[2,3-b]pyridine-1-carboxylate was obtained. MS m/z=403 [M+1]+. Calcd for C23H22N4O3: 402.17.

Workup

  1. customIn an argon-purged
  2. customsealed tube
  3. customThe tube was sealed
  4. temperatureheated to 100° C
  5. waitAfter 1 h 45 min
  6. temperatureThe reaction mixture was cooled to rt
  7. washwashing with EtOAc
  8. dry with materialThe filtrate was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by column chromatography on 120 g silica gel column
  12. custom(90:10:1 DCM:MeOH:NH4OH) to flush out the nonpolar spots
  13. custom80:20 DCM:(90:10:1 DCM:MeOH:NH4OH) to collect the Boc-product
  14. customA viscous brown oil was obtained
  15. customat rt
  16. customfor several hours
  17. customsmall amounts of crystaline colonies were formed
  18. temperatureThe oil was cooled to 0° C.
  19. customlight yellow solid precipitated out
  20. additionafter adding small amounts of hexanes
  21. additiona little bit of ether in addition
  22. filtrationThe light yellow solid was filtered
  23. washwashed with cold hexanes
  24. customdried under vacuum

Sources & evidence

ORD record
ord-731f16c494344977a16838d401df8d57
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Reaction notes

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