Boron tribromide → HCID 178508190, compound

HRID 2192234Notes

Reaction equation

HRID 2192234 reaction equation
[CH2:1]([N:8]1[C:20]2[C:19]3[N:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:13]=[C:12]([NH2:21])[C:11]=2[N:10]=[C:9]1[O:22]CC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>ClCCl>[NH2:21][C:12]1[C:11]2[N:10]=[C:9]([OH:22])[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:20]=2[C:19]2[N:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:13]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide2×HCID 16742453HCID 16742453, compound

Product 1

HCID 178508190HCID 178508190, compoundYield 16.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 1-benzyl-2-ethoxy-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (1.3 g, 4 mmol) in dichloromethane (20 mL) was added boron tribromide (1M solution in dichloromethane, 10 mL, 10 mmol), and the reaction was stirred at room temperature. Additional aliquots of the boron tribromide solution (7.5 equivalents, 30 mmol total) were added to drive the reaction to completion. The reaction was concentrated under reduced pressure, and to it was added methanol (1 mL) followed by 6M HCl (100 mL). The reaction was heated at 50° C. for 2 hours, cooled in an ice bath, and adjusted to a basic pH by the addition of 6N NaOH. The product was extracted with dichloromethane and the organic layers were combined, dried (MgSO4), filtered, and evaporated to afford crude product. The product was purified by preparative HPLC (Analogix Separation System, and eluted with a gradient of 0-10% methanol in dichloromethane with 1% ammonium hydroxide) to provide a solid which was triturated with hot acetonitrile, filtered, and washed with ether to afford 4-amino-1-benzyl-1H-imidazo[4,5-c][1,5]naphthyridin-2-ol (196 mg) as a yellow solid, mp>250° C.; HRMS (ESI) calcd for C16H13N5O[M+H]+: 292.1198. found 292.1198.

Workup

  1. customthe reaction to completion
  2. concentrationThe reaction was concentrated under reduced pressure
  3. additionto it was added methanol (1 mL)
  4. temperatureThe reaction was heated at 50° C. for 2 hours
  5. temperaturecooled in an ice bath
  6. additionadjusted to a basic pH by the addition of 6N NaOH
  7. extractionThe product was extracted with dichloromethane
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customto afford crude product
  12. customThe product was purified by preparative HPLC (
  13. customAnalogix Separation System
  14. washeluted with a gradient of 0-10% methanol in dichloromethane with 1% ammonium hydroxide)
  15. customto provide a solid which
  16. customwas triturated with hot acetonitrile
  17. filtrationfiltered
  18. washwashed with ether

Sources & evidence

ORD record
ord-c831c18c07c04e69b7b3eda5f32d0c83
Source dataset
uspto-grants-2012_12
Patent number
US08329721B2

Reaction notes

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