Cesium carbonate → (R)-6-(4-chlorophenyl)-8-(1,5-dimethyl-1H-pyrazol-4-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

HRID 1485441Notes

Reaction equation

HRID 1485441 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][N:26]1[C:30]([CH3:31])=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=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]([C:29]4[CH:28]=[N:27][N:26]([CH3:25])[C:30]=4[CH3:31])=[CH:24][C:6]2=3)=[CH:22][CH:21]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 426473131,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 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 70979282(R)-6-(4-chlorophenyl)-8-(1,5-dimethyl-1H-pyrazol-4-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepineYield 23.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °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 (41 mg, 0.1 mmol), 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (34 mg, 0.15 mmol), tetrakis(triphenylphosphine)palladium(0) (12 mg) and cesium carbonate (65 mg, 0.2 mmol) in toluene, ethanol and water (5 mL, 4:2:1) was stirred at 100° C. for 0.5 hour under microwave (pressure: 3.2 bar, equipment power: 150 W). The reaction mixture was evaporated, water (10 mL) was added and the mixture was extracted with ethyl acetate (20 mL). 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)-6-(4-chlorophenyl)-8-(1,5-dimethyl-1H-pyrazol-4-yl)-1,4-dimethyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine as a yellow solid (10 mg, 23%).

Workup

  1. customThe reaction mixture was evaporated
  2. additionwater (10 mL) was added
  3. extractionthe mixture was extracted with ethyl acetate (20 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue which
  8. customwas purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1)

Sources & evidence

ORD record
ord-d15dc16a4af247e296db367144d45c55
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

Loading…