Dimethylformamide → 5-(2-fluorophenyl)-7-(4-pyridinyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

HRID 1365060Notes

Reaction equation

HRID 1365060 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][NH:8][CH:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[F:18])[C:6]=2[CH:19]=1.[N:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH:7]1[C:6]2[CH:19]=[C:2]([C:23]3[CH:24]=[CH:25][N:20]=[CH:21][CH:22]=3)[CH:3]=[CH:4][C:5]=2[NH:11][CH2:10][CH2:9][NH:8]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 577324237-bromo-5-(2-fluorophenyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

Product 1

HCID 117024835-(2-fluorophenyl)-7-(4-pyridinyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepineYield 40.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A 5-mL microwave tube was charged with provided 7-bromo-5-(2-fluorophenyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine (25 mg), 4-pyridylboronic acid (50 mg), dichlorobis(triphenyl-phosphine)palladium(II) (10 mg), potassium carbonate (50 mg), dimethylformamide (3.5 mL) and water (0.5 mL). The reaction was heated to 160° C. for 360 seconds using microwave irradiation. The reaction was concentrated to dryness and the residue was taken up in water and extracted with ethyl acetate. The organic extracts were combined and dried over magnesium sulfate. The drying agent was filtered and the filtrate was concentrated to an oil. Silica gel purification provided the title compound 5-(2-fluorophenyl)-7-(4-pyridinyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine (10 mg) as a white powder. H1 NMR (d6-dmso): 8.42 (d, 2H), 7.46 (m, 2H), 7.30 (m, 3H), 7.18 (m, 2H), 7.02 (d, 1H), 6.83 (s, 1H), 5.85 (br s, 1H), 5.22 (br s, 1H), 3.18-3.3 (m, 1H), 2.78-2.96 (m, 3H), 2.64 (br s, 1H). Mass (ES+)=320.2 (100%).

Workup

  1. custommicrowave irradiation
  2. concentrationThe reaction was concentrated to dryness
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe drying agent was filtered
  6. concentrationthe filtrate was concentrated to an oil
  7. customSilica gel purification

Sources & evidence

ORD record
ord-58fe06951f1b4a4894b1d88bed11439b
Source dataset
uspto-grants-2011_02
Patent number
US07888503B2

Reaction notes

Loading…