5-Fluoro-2-nitropyridine → (R)-8-bromo-1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

HRID 1485450Notes

Reaction equation

HRID 1485450 reaction equation
F[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[Br:11][C:12]1[CH:13]=[CH:14][C:15]2[N:21]3[C:22]([CH3:25])=[N:23][N:24]=[C:20]3[C@H:19]([CH3:26])[CH2:18][NH:17][C:16]=2[CH:27]=1.C([O-])(C)(C)C.[K+]>CS(C)=O.O>[Br:11][C:12]1[CH:13]=[CH:14][C:15]2[N:21]3[C:22]([CH3:25])=[N:23][N:24]=[C:20]3[C@H:19]([CH3:26])[CH2:18][N:17]([C:2]3[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=3)[C:16]=2[CH:27]=1

Participants

6

Reactant 3

HCID 167481095-Fluoro-2-nitropyridineHCID 23665647Potassium tert-butoxideHCID 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 70979064(R)-8-bromo-1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepineYield 77.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-fluoro-2-nitropyridine (284 mg, 2 mmol) and (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) in dimethyl sulfoxide (5 mL) was added potassium tert-butanolate (223 mg, 2 mmol). The reaction mixture was heated at 120° C. for 1 hour under microwave (pressure: 3.2 bar, equipment power: 150 W). The mixture was diluted with water (50 mL), extracted with ethyl acetate (20 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to give a residue which was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1) to give (R)-8-bromo-1,4-dimethyl-6-(6-nitropyridin-3-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (320 mg, 77%) as a light yellow solid.

Workup

  1. extractionextracted with ethyl acetate (20 mL×3)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue which
  6. customwas purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1)

Sources & evidence

ORD record
ord-957364c5b8f24484978aecfa0399db18
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

Loading…