Pyridine → 3-(3-bromo-2-methylphenyl)-1-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione

HRID 523278Notes

Reaction equation

HRID 523278 reaction equation
[Br:1][C:2]1[C:3]([CH3:16])=[C:4]([N:8]2[C:13](=[O:14])[CH:12]=[CH:11][NH:10][C:9]2=[O:15])[CH:5]=[CH:6][CH:7]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[C:3]([CH3:16])=[C:4]([N:8]2[C:13](=[O:14])[CH:12]=[CH:11][N:10]([C:21]3[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=3)[C:9]2=[O:15])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 2856454-Fluorophenylboronic acidHCID 1177608363-(3-bromo-2-methylphenyl)pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1177611823-(3-bromo-2-methylphenyl)-1-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dioneYield 64.4%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A stirred suspension of copper(II) acetate (0.543 g, 2.99 mmol), 3-(3-bromo-2-methylphenyl)pyrimidine-2,4(1H,3H)-dione (0.42 g, 1.49 mmol), (4-fluorophenyl) boronic acid (0.418 g, 2.99 mmol), and activated molecular sieves (750 mg) in dry DCM (25 mL) was treated with pyridine (0.363 mL, 4.48 mmol) and stirred at room temperature overnight. The mixture was diluted with DCM, filtered through CELITE®, and the solids were washed with DCM and THF. The combined filtrates were washed with water, dried and concentrated. The residue was purified by column chromatography on silica gel (40 g), eluting with EtOAc-hexanes (gradient from 20-40%), to give 3-(3-bromo-2-methylphenyl)-1-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione as a yellow glassy solid (0.36 g, 43% yield). Mass spectrum m/z 375, 377 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J=7.9 Hz, 1H), 7.68 (dd, J=7.9, 1.3 Hz, 1H), 7.60-7.51 (m, 2H), 7.40-7.22 (m, 4H), 5.95 (d, J=7.9 Hz, 1H), 2.21-2.12 (m, 3H).

Workup

  1. filtrationfiltered through CELITE®
  2. washthe solids were washed with DCM and THF
  3. washThe combined filtrates were washed with water
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (40 g)
  7. washeluting with EtOAc-hexanes (gradient from 20-40%)

Sources & evidence

ORD record
ord-57b33034c6f64e2fbf4cc32495a30ed9
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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