Dimethylformamide → 7-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine

HRID 1365074Notes

Reaction equation

HRID 1365074 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:18]=1.CN(C)C=O.[F:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][C:30]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>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:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][C:30]=1[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:18]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27793533-Fluoropyridine-4-boronic acidHCID 215088487-bromo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine

Product 1

HCID 116382827-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A 5 mL microwave tube was charged with 7-bromo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine (50 mg), dimethylformamide (3.5 mL), 3-fluoro-4-pyridylboronic acid (2 equiv), potassium carbonate (2 equiv), bis(triphenylphosphine)-palladiumdichloride (10 mol %), and water (0.7 mL). The mixture was heated in a microwave at 150° C. for 5 min, then cooled and concentrated to dryness. The residue was taken up in ethyl acetate and filtered through a Celite pad. The filtrate was concentrated to dryness and the residue was triturated in diethyl ether. The resulting solids were collected on filter then purified using preparative thin-layer chromatography. The plates were eluted with 12.5% methanol in chloroform, and the desired band was collected to provide 7-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine as a yellow powder. H1 NMR (d6-dmso): 8.45 (d, 1H), 8.32 (d, 1H), 7.52 (d, 1H), 7.46 (m, 2H), 7.36-7.42 (m, 4H), 7.21 (s, 1H), 6.91 (d, 1H), 6.78 (brt, 1H), 3.96 (m, 2H), 3.60 (m, 2H).

Workup

  1. temperaturecooled
  2. concentrationconcentrated to dryness
  3. filtrationfiltered through a Celite pad
  4. concentrationThe filtrate was concentrated to dryness
  5. customthe residue was triturated in diethyl ether
  6. customThe resulting solids were collected
  7. filtrationon filter
  8. customthen purified
  9. washThe plates were eluted with 12.5% methanol in chloroform
  10. customthe desired band was collected

Sources & evidence

ORD record
ord-34b75436bf7245629f3d40a2196c9947
Source dataset
uspto-grants-2011_02
Patent number
US07888503B2

Reaction notes

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