Nitrogen → (R)-8-bromo-1,4-dimethyl-6-(4-(methylsulfonyl)phenyl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

HRID 1485454Notes

Reaction equation

HRID 1485454 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[C@H:9]([CH3:16])[CH2:8][NH:7][C:6]=2[CH:17]=1.I[C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.N#N>CC1C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[C@H:9]([CH3:16])[CH2:8][N:7]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[C:6]=2[CH:17]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 46689421-Iodo-4-(methylsulfonyl)benzene2×HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 70978878(R)-8-bromo-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

Product 1

HCID 70979131(R)-8-bromo-1,4-dimethyl-6-(4-(methylsulfonyl)phenyl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepineYield 39.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (R)-8-bromo-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (100 mg, 0.34 mmol) in Methylbenzene (5 mL), were added 1-iodo-4-(methylsulfonyl)benzene (115.2 mg, 0.40 mmol) and 1-iodo-4-(methylsulfonyl)benzene (115.2 mg, 0.40 mmol). Cs2CO3 (222.3 mg, 0.68 mmol), tris(dibenzylideneacetone)dipalladium(0) (31.4 mg, 0.03 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (39.22 mg, 0.07 mmol) were added. The mixture was via vacuo/N2 and stirred at 90° C. for 18 h under N2 atmosphere. After concentration, the mixture was poured into water (10 mL) and extracted with dichloromethane (20 mL×3). The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated and purified by prep-TLC (elute: DCM:CH3OH=10:1) to give (R)-8-bromo-1,4-dimethyl-6-(4-(methylsulfonyl)phenyl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (60 mg, 39%).

Workup

  1. concentrationAfter concentration
  2. additionthe mixture was poured into water (10 mL)
  3. extractionextracted with dichloromethane (20 mL×3)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by prep-TLC (elute: DCM:CH3OH=10:1)

Sources & evidence

ORD record
ord-51e4fcbce48844ed95369f54ab42f7ba
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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