2,2'-Bipyridine → HCID 67469070, compound

HRID 1476439Notes

Reaction equation

HRID 1476439 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[N:7][NH:8][C:9]=2[CH:10]=1.[CH:15]1(B(O)O)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+].N1C=CC=CC=1C1C=CC=CN=1.[NH4+].[Cl-]>ClCCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[N:7][N:8]([CH:15]3[CH2:17][CH2:16]3)[C:9]=2[CH:10]=1

Participants

9

Reactant 5

HCID 14742,2'-BipyridineHCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 2760897Cyclopropylboronic acidHCID 24728062methyl 6-bromo-1H-indazole-4-carboxylate

Product 1

HCID 67469070HCID 67469070, compound

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 6-bromo-1H-indazole-4-carboxylate (1.0 g, 3.92 mmol) was dissolved in 1,2-Dichloroethane (DCE) (14 mL) and stirred for 15 min. Next added cyclopropylboronic acid (0.674 g, 7.84 mmol) and sodium carbonate (0.831 g, 7.84 mmol). The reaction was stirred at RT (suspension). Copper (II) acetate (0.712 g, 3.92 mmol) and 2,2′-bipyridine (0.612 g, 3.92 mmol) were suspended in DCE (24 mL) with heating and the hot suspension was added to the reaction mixture. The contents were stirred with heating at 70° C. overnight. After cooling to RT, the reaction mixture was poured onto sat. NH4Cl and ice. Next added DCM and stirred for 10 min. The contents were filtered through Celite, washing with water and DCM. The layers were separated and the aq. layer was extracted with DCM (1×). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography (3-25% gradient ethyl acetate in hexanes) wherein the less polar product was observed to be the title compound, and was collected as a yellow solid (0.54 g, 46%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-1.20 (m, 4H), 3.81-3.90 (m, 1H), 3.95 (s, 3H), 7.86 (d, J=1.52 Hz, 1H), 8.30 (d, J=1.77 Hz, 1H), 8.32 (d, J=1.01 Hz, 1H); LC-MS (ES) m/z=295.1 [M+H]

Workup

  1. stirringThe reaction was stirred at RT (suspension)
  2. temperaturewith heating
  3. additionthe hot suspension was added to the reaction mixture
  4. stirringThe contents were stirred
  5. temperatureAfter cooling to RT
  6. stirringstirred for 10 min
  7. filtrationThe contents were filtered through Celite
  8. washwashing with water and DCM
  9. customThe layers were separated
  10. extractionthe aq. layer was extracted with DCM (1×)
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude product was purified by silica gel chromatography (3-25% gradient ethyl acetate in hexanes) wherein the less polar product
  16. customwas collected as a yellow solid (0.54 g, 46%)

Sources & evidence

ORD record
ord-f5727ee8994142a9854126fd7672eea8
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

Loading…