Diisopropylamine → 5-(2,3-Difluorophenyl)-1-(2-methoxyethyl)-3-nitropyridin-2(1H)-one

HRID 20175

Reaction equation

HRID 20175 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[C:5](=[O:12])[N:6]([CH2:8][CH2:9][O:10][CH3:11])[CH:7]=1.[F:16][C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.C(NC(C)C)(C)C.[Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:16][C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1[C:2]1[CH:3]=[C:4]([N+:13]([O-:15])=[O:14])[C:5](=[O:12])[N:6]([CH2:8][CH2:9][O:10][CH3:11])[CH:7]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 222932795-Bromo-1-(2-methoxyethyl)-3-nitropyridin-2(1H)-one

Product 1

HCID 222931735-(2,3-Difluorophenyl)-1-(2-methoxyethyl)-3-nitropyridin-2(1H)-oneYield 59.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Palladium acetate (41.0 mg, 0.18 mmol) was added to a solution of 5-bromo-1-(2-methoxyethyl)-3-nitropyridin-2(1H)-one (500 mg, 1.81 mmol), 2,3-difluorophenyl boronic acid (570 mg, 3.61 mmol), diisopropylamine (0.759 mL, 5.41 mmol) and 3,3′,3″-phosphinidynetris(benzenesulfonic acid) trisodium salt (310 mg, 0.541 mmol), in N,N-dimethylformamide (15 mL) and water (5 mL) and heated to 80° C. After 2 h, the mixture was allowed to cool to ambient temperature and filtered. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (335 mg). MS 311 (M+1). 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J=2.7 Hz, 1H), 8.03 (d, J=2.4 Hz, 1H), 7.23-7.18 (m, 2H), 7.15-7.12 (m, 1H), 4.33 (t, J=4.8 Hz, 2H), 3.74 (t, J=4.8 Hz, 2H), 3.35 (s, 3H).

Workup

  1. filtrationfiltered
  2. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-603d6f3f4e5349fbacc3acff1172a14e
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Linked notes

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