Cesium carbonate → HCID 68556217, compound

HRID 508707Notes

Reaction equation

HRID 508707 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[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:51]1[N:52]=[N:53][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:55][CH:56]=1>CN(C=O)C.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>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:6]2[C:5]3[CH:19]=[CH:20][C:2]([C:51]4[N:52]=[N:53][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:55][CH:56]=4)=[CH:3][C:4]=3[CH2:10][N:9]([CH3:11])[CH2:8][CH2:7]2)=[CH:13][CH:14]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 282425263-Chloro-6-(trifluoromethyl)pyridazineHCID 68560867HCID 68560867, compound

Product 1

HCID 68556217HCID 68556217, compoundYield 80.2%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A round bottomed flask was charged with 7-bromo-1-(4-fluorophenyl)-4-methyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (75 mg, 0.22 mmol) from step A above, bis(pinacolato)diboron (62 mg, 0.25 mmol) and potassium acetate (66 mg, 0.67 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (16 mg, 0.02 mmol) in DMF (1 mL). The mixture was refilled with nitrogen three times and then stirred at 65° C. overnight. The mixture was cooled to room temperature. Cesium carbonate (219 mg, 0.67 mmol), 3-chloro-6-trifluoromethylpyridazine (49 mg, 0.67 mmol), and water (0.5 mL) were added. The mixture was refilled with nitrogen three times 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 extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (100:0 to 10:1 methylene chloride/methanol) to yield the desired 1-(4-fluorophenyl)-4-methyl-7-(6-(trifluoromethyl)pyridazin-3-yl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine (71 mg, 79%) as a grey solid

Workup

  1. additionThe mixture was refilled with nitrogen three times
  2. temperatureThe mixture was cooled to room temperature
  3. additionThe mixture was refilled with nitrogen three times
  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. dry with materialThe combined extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography (100:0 to 10:1 methylene chloride/methanol)

Sources & evidence

ORD record
ord-bdbe85fdfbfd4067927668321484d31a
Source dataset
uspto-grants-2015_08
Patent number
US09096546B2

Reaction notes

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