Cesium carbonate → HCID 68560145, compound

HRID 508706Notes

Reaction equation

HRID 508706 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]2[N:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:7][CH2:8][N:9]([CH3:11])[CH2:10][C:4]=2[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:50]1[N:51]=[N:52][C:53]([CH3:56])=[CH:54][CH:55]=1>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O.CN(C=O)C>[CH3:11][N:9]1[CH2:10][C:4]2[CH:3]=[C:2]([C:50]3[N:51]=[N:52][C:53]([CH3:56])=[CH:54][CH:55]=3)[CH:19]=[CH:18][C:5]=2[N:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:8]1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 2272543-Chloro-6-methylpyridazineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 68555319HCID 68555319, compound

Product 1

HCID 68560145HCID 68560145, compoundYield 69.2%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A round bottomed flask was charged with 7-bromo-4-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (0.22 g, 0.7 mmol) from step A above, bis(pinacolato)diboron (0.20 g, 0.77 mmol), potassium acetate (0.21 g, 2.1 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (57 mg, 0.07 mmol) and DMF (3.5 mL). The mixture was degassed with nitrogen (3×) and then stirred at 60° C. overnight. The mixture was cooled to room temperature, and cesium carbonate (0.68 g, 2.1 mmol), 3-chloro-6-methylpyridazine (0.14 g, 1.1 mmol) and water (1.8 mL) were added to it. The mixture was degassed with nitrogen (3×) and then stirred at 60° C. for 3 hours. After cooling, the mixture was partitioned between methylene chloride and water. The aqueous phase was extracted with methylene chloride (3×20 mL). The combined organic extract was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (methylene chloride, then 10:1 methylene chloride/methanol) to yield the desired 4-methyl-7-(6-methylpyridazin-3-yl)-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (0.16 g, 67%) as a grey solid.

Workup

  1. customThe mixture was degassed with nitrogen (3×)
  2. temperatureThe mixture was cooled to room temperature
  3. customThe mixture was degassed with nitrogen (3×)
  4. stirringstirred at 60° C. for 3 hours
  5. temperatureAfter cooling
  6. customthe mixture was partitioned between methylene chloride and water
  7. extractionThe aqueous phase was extracted with methylene chloride (3×20 mL)
  8. extractionThe combined organic extract
  9. dry with materialwas dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography (methylene chloride

Sources & evidence

ORD record
ord-7852c2c965af49449230e308baafba51
Source dataset
uspto-grants-2015_08
Patent number
US09096546B2

Reaction notes

Loading…