Boron tribromide → HCID 59436049, compound

HRID 1802488Notes

Reaction equation

HRID 1802488 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][N:23]=[C:24]([O:25]CC)[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1.ClC1C2C3C(=CC=NC=3)N=C(NC3C(F)=CC(F)=CC=3Cl)C=2C=CN=1.C[O-].[Na+].B(Br)(Br)Br>CO>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][NH:23][C:24](=[O:25])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1

Participants

6

Reactant 4

HCID 25134Boron tribromideHCID 10942334Sodium MethoxideHCID 59436014HCID 59436014, compoundHCID 59436106HCID 59436106, compound

Product 1

HCID 59436049HCID 59436049, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-(2-chloro-4,6-difluorophenyl)-10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-amine and 10-chloro-N-(2-chloro-4,6-difluorophenyl)pyrido[4,3-c]-1,6-naphthyridin-6-amine (1.3 g) in 8 mL methanol was added sodium methoxide (5 mL, 2.06 mmol, 25% weight in methanol) and the mixture was heated to 100° C. for 1 hr. The solution was cooled to room temperature, concentrated, and redissolved with 3:1 CHCl3/i-PrOH followed by a wash with saturated NH4Cl. The organic layers were combined, dried with MgSO4, filtered, and concentrated under reduced pressure. A portion of the crude solution (540 mg) was taken up in CHCl3 (8 mL) and boron tribromide (1M in CH2Cl2, 7 mL, 7.0 mmol) and heated to 85° C. for 1 hr. The solution was cooled to room temperature, extracted with 3:1 CHCl3/i-PrOH, and washed with saturated NaHCO3. The organic layers were dried with MgSO4, filtered, and concentrated to afford the crude product. The crude residue was purified on silica gel (100% CH2Cl2 to 25% MeOH, gradient elution) which afforded the title compound.

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutionredissolved with 3:1 CHCl3/i-PrOH
  4. washa wash with saturated NH4Cl
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. temperatureThe solution was cooled to room temperature
  9. extractionextracted with 3:1 CHCl3/i-PrOH
  10. washwashed with saturated NaHCO3
  11. dry with materialThe organic layers were dried with MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto afford the crude product
  15. customThe crude residue was purified on silica gel (100% CH2Cl2 to 25% MeOH, gradient elution) which

Sources & evidence

ORD record
ord-0f8cc2bc16d14e43826db59610443758
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

Loading…