Boron tribromide → HCID 59436022, compound

HRID 1802495Notes

Reaction equation

HRID 1802495 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl: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.[NH:28]1[C:32](B(O)O)=[CH:31][CH:30]=[N:29]1.C([O-])(O)=O.[Na+].B(Br)(Br)Br>C(Cl)(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:9][C:4]1[CH:5]=[C:6]([C:30]2[NH:29][N:28]=[CH:32][CH:31]=2)[CH:7]=[C:2]([Cl:1])[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

7

Reactant 4

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 112519791H-Pyrazole-5-boronic acidHCID 59436035HCID 59436035, compound

Product 1

HCID 59436022HCID 59436022, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-(2,6-dichloro-4-iodophenyl)-10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (200 mg, 0.40 mmol) were added 1H-pyrazol-5-ylboronic acid (48 mg, 0.43 mmol) 2.0 M solution of NaHCO3 (1 mL) and tetrakis(triphenylphosphine)palladium (0) (90 mg, 0.78 mmol) and the mixture was heated to 80° C. for 4 hr. After cooling to room temperature, the reaction mixture was extracted with EtOAc and water. Column chromatography (100% Hex to 100% EtOAc) afforded the cross-coupled product. This purified material (79 mg) was taken up in chloroform (5 mL) followed by the addition of BBr3 (1.40 mL, 1M in CH2Cl2) and heated to 85° C. for 1 hr. The solution was cooled to room temperature, extracted with 3:1 CHCl3/IPrOH and washed with saturated NaHCO3. The organic layers were dried with MgSO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (100% CH2Cl2 to 35% MeOH/65% CH2Cl2) afforded the title compound as a mixture of rotamers.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe reaction mixture was extracted with EtOAc and water
  3. customColumn chromatography (100% Hex to 100% EtOAc) afforded the cross-coupled product
  4. temperatureheated to 85° C. for 1 hr
  5. temperatureThe solution was cooled to room temperature
  6. extractionextracted with 3:1 CHCl3/IPrOH
  7. washwashed with saturated NaHCO3
  8. dry with materialThe organic layers were dried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by column chromatography (100% CH2Cl2 to 35% MeOH/65% CH2Cl2)

Sources & evidence

ORD record
ord-aadfe25a969642369bfbc4297e099c6a
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

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