1H-1,2,4-Triazole → (4R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(1,2,4-triazol-1-yl)-4,5-dihydro-[1,2,4]triazolo[3,4-d][1,5]benzodiazepine

HRID 1485440Notes

Reaction equation

HRID 1485440 reaction equation
Br[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:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:6]=2[CH:24]=1.[NH:25]1[CH:29]=[N:28][CH:27]=[N:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.O.[Cu]I>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([N:7]2[CH2:8][C@@H:9]([CH3:16])[C:10]3=[N:14][N:13]=[C:12]([CH3:15])[N:11]3[C:5]3[CH:4]=[CH:3][C:2]([N:25]4[CH:29]=[N:28][CH:27]=[N:26]4)=[CH:24][C:6]2=3)=[CH:18][CH:19]=1

Participants

7

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 10796Cesium carbonateHCID 70979089(R)-8-bromo-6-(4-chlorophenyl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

Product 1

HCID 71465611(4R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(1,2,4-triazol-1-yl)-4,5-dihydro-[1,2,4]triazolo[3,4-d][1,5]benzodiazepineYield 25.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (R)-8-bromo-6-(4-chlorophenyl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (40.2 mg, 0.1 mmol), 1H-1,2,4-triazole (13.8 mg, 0.2 mmol), copper(I) iodide (3.8 mg, 0.02 mmol), and cesium carbonate (59 mg, 0.18 mmol) in N-methyl-2-pyrrolidone (3 mL) was stirred at 150° C. for 16 hours. The mixture was diluted with water (10 mL), extracted with ethyl acetate (3*20 mL). The combined organic layer was washed with water (3*20 mL) and brine (3*20 mL) in turns, dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by prep-TLC (silica-gel, dichloromethane/methanol=15:1) to give (R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(1H-1,2,4-triazol-1-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine as a white solid (10 mg, 25.7%).

Workup

  1. extractionextracted with ethyl acetate (3*20 mL)
  2. washThe combined organic layer was washed with water (3*20 mL) and brine (3*20 mL) in turns
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue
  7. customThe residue was purified by prep-TLC (silica-gel, dichloromethane/methanol=15:1)

Sources & evidence

ORD record
ord-c406c6c3e52f477a8023f1365da521b4
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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