1,10-Phenanthroline → (4R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(5-methyl-1,2,4-triazol-1-yl)-4,5-dihydro-[1,2,4]triazolo[3,4-d][1,5]benzodiazepine

HRID 1485442Notes

Reaction equation

HRID 1485442 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.[CH3:25][C:26]1[N:30]=[CH:29][NH:28][N:27]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C.[Cu]I>[Cl:23][C:20]1[CH:19]=[CH:18][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:27]4[C:26]([CH3:25])=[N:30][CH:29]=[N:28]4)=[CH:24][C:6]2=3)=[CH:22][CH:21]=1.[Cl:23][C:20]1[CH:19]=[CH:18][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:28]4[CH:29]=[N:30][C:26]([CH3:25])=[N:27]4)=[CH:24][C:6]2=3)=[CH:22][CH:21]=1

Participants

9

Reactant 4

HCID 13181,10-PhenanthrolineHCID 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]diazepineHCID 178433329HCID 178433329, compound

Product 2

HCID 70979147(4R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(5-methyl-1,2,4-triazol-1-yl)-4,5-dihydro-[1,2,4]triazolo[3,4-d][1,5]benzodiazepineYield 25%HCID 70979371(R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(3-methyl-1H-1,2,4-triazol-1-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepineYield 13%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °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 (60 mg, 0.15 mmol), 3-methyl-1H-1,2,4-triazole (14 mg, 0.16 mmol), copper (I) iodide (6 mg, 0.03 mmol), 1,10-phenanthroline (11 mg, 0.06 mmol) and cesium carbonate (98 mg, 0.3 mmol) in dimethyl sulfoxide (3 mL) was heated at 130° C. for 30 minutes under microwave (pressure: 1.0 bar, equipment power: 150 W). The reaction mixture was diluted with ethyl acetate (20 mL) and washed with brine (10 mL×3). The organic phase was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated to give a crude product which was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to afford (R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(5-methyl-1H-1,2,4-triazol-1-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (15 mg, 25%) and (R)-6-(4-chlorophenyl)-1,4-dimethyl-8-(3-methyl-1H-1,2,4-triazol-1-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (8 mg, 13%) as a light yellow solid.

Workup

  1. washwashed with brine (10 mL×3)
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give a crude product which
  6. customwas purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-03e61344b64646148a19bfc0a91c07ab
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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