1,10-Phenanthroline → (R)-8-bromo-1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

HRID 1485448Notes

Reaction equation

HRID 1485448 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:20]=[N:21][N:22]([CH3:24])[CH:23]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.C(OCC)(=O)C.[Cu]I>[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:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[C:6]=2[CH:17]=1

Participants

8

Reactant 4

HCID 13181,10-PhenanthrolineHCID 62657Potassium Phosphate, TribasicHCID 27347731-Methyl-4-iodo-1H-pyrazoleHCID 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 70979194(R)-8-bromo-1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

A mixture of (R)-8-bromo-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (292 mg, 1 mmol), 4-iodo-1-methyl-1H-pyrazole (312 mg, 1.5 mmol), copper (I) iodide (58 mg, 0.3 mmol), 1,10-phenanthroline (54 mg, 0.3 mmol) and potassium phosphate (424 mg, 2 mmol) in dimethyl sulfoxide (10 mL) was heated at 150° C. for 14 hours under nitrogen. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with brine (20 mL×3). The organic phase was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated to give (R)-8-bromo-1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine which was used in the next step without further purification. LRMS (M+H)+: calcd 372.07. found 372.

Workup

  1. washwashed with brine (20 mL×3)
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-af1179fc72294261a5c0a9c5257ed6dd
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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