2,2'-Bipyridine → 4-(benzyloxy)-6-chloro-3-cyclopropyl-3H-imidazo[4,5-c]pyridine

HRID 2209007Notes

Reaction equation

HRID 2209007 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[NH:15][CH:16]=[N:17][C:13]=2[CH:12]=[C:11]([Cl:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.C([O-])([O-])=O.[Na+].[Na+].B(O)O.N1C=CC=CC=1C1C=CC=CN=1>ClCCCl.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Cu+2]>[CH2:1]([O:8][C:9]1[C:14]2[N:15]([CH:19]3[CH2:21][CH2:20]3)[CH:16]=[N:17][C:13]=2[CH:12]=[C:11]([Cl:18])[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 14742,2'-BipyridineHCID 10340Sodium Carbonate4×HCID 61668Boronic Acid3×HCID 2760897Cyclopropylboronic acidHCID 178477827HCID 178477827, compound

Product 1

HCID 1178430004-(benzyloxy)-6-chloro-3-cyclopropyl-3H-imidazo[4,5-c]pyridine

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

In a separate flask 4-(benzyloxy)-6-chloro-3H-imidazo[4,5-c]pyridine 2.24 (502 mg, 1.93 mmol), cyclopropane boronic acid (334 mg, 3.89 mmol) and Na2CO3 (415 mg, 3.9 mmol) were taken up in 1,2-DCE (13 mL). The aforementioned catalyst mixture was then added to this mixture, washing with 4×1 mL 1,2-DCE. The resulting mixture was heated to 70° C. and was stirred open to the air. After 7 h, additional Na2CO3 (215 mg, 2.03 mmol) and boronic acid (170 mg, 2.0 mmol) were added along with a heated suspension of Cu(OAc)2 (182 mg, 1.0 mmol) and 2,2′-bipyridine (155 mg, 0.99 mmol) in 1,2-DCE (3 mL). After an additional 1.5 h, additional boronic acid (340 mg, 4.0 mmol) and Na2CO3 (415 mg, 3.9 mmol) were added and the reaction was capped and stirred overnight. After an additional 14.5 h, additional boronic acid (150 mg, 1.7 mmol) and Na2CO3 (215 mg, 2.03 mmol) were added and the mixture was stirred open to air. After an additional 1.5 h, the reaction mixture was cooled to r.t., was diluted with EtOAc (75 mL), and was filtered through Celite. The filtrate was washed with half-saturated aqueous NH4Cl (75 mL), water (50 mL), and brine (50 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. Purification by silica gel chromatography (0% to 5% THF in DCM) provided 4-(benzyloxy)-6-chloro-3-cyclopropyl-3H-imidazo[4,5-c]pyridine 2.35.

Workup

  1. additionThe aforementioned catalyst mixture was then added to this mixture
  2. washwashing with 4×1 mL 1,2-DCE
  3. waitAfter an additional 1.5 h
  4. customthe reaction was capped
  5. stirringstirred overnight
  6. waitAfter an additional 14.5 h
  7. stirringthe mixture was stirred open to air
  8. waitAfter an additional 1.5 h
  9. temperaturethe reaction mixture was cooled to r.t.
  10. filtrationwas filtered through Celite
  11. washThe filtrate was washed with half-saturated aqueous NH4Cl (75 mL), water (50 mL), and brine (50 mL)
  12. dry with materialThe organic phase was dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customPurification by silica gel chromatography (0% to 5% THF in DCM)

Sources & evidence

ORD record
ord-c393bf07b92443a58e7fb724b84ef202
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…