Dichloromethane → N-benzyl-3-methyl-5-(2-oxo-4-phenethylpyridin-1(2H)-yl)thiophene-2-carboxamide

HRID 1887371Notes

Reaction equation

HRID 1887371 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][N:10]([C:13]2[S:14][C:15]([C:19](=[O:28])[NH:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:16]([CH3:18])[CH:17]=2)[C:9](=[O:29])[CH:8]=1)(=O)=O.[CH2:32](B(O)O)[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:21]([NH:20][C:19]([C:15]1[S:14][C:13]([N:10]2[CH:11]=[CH:12][C:7]([CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:8][C:9]2=[O:29])=[CH:17][C:16]=1[CH3:18])=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 65389Phenylethane Boronic AcidHCID 57744501HCID 57744501, compound

Product 1

HCID 57744497N-benzyl-3-methyl-5-(2-oxo-4-phenethylpyridin-1(2H)-yl)thiophene-2-carboxamideYield 40%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(5-(benzylcarbamoyl)-4-methylthiophen-2-yl)-2-oxo-1,2-dihydropyridin-4-yl trifluoromethanesulfonate (0.15 g, 0.32 mmol), phenethyl boronic acid (0.047 g, 0.31 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), 1:1 complex with dichloromethane (0.023 g, 0.028 mmol) and potassium carbonate (0.13 g, 0.95 mmol) in tetrahydrofuran (3 mL) and water (0.3 mL) was stirred in a sealed tube at 70° C. for 16 hours under nitrogen atmosphere. The reaction mixture was allowed to cool to ambient temperature, and was partitioned between ethyl acetate (75 mL) and water (35 mL). The organic layer was washed sequentially with 10% aqueous hydrochloric acid (30 mL), saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (30 mL), then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 20% ethyl acetate in dichloromethane to afford the title compound as a light cream color solid in 40% yield (0.054 g): mp 145-146° C.; 1H NMR (300 MHz, CDCl3) δ 7.59 (d, J=7.3 Hz, 1H), 7.38-7.15 (m, 10H), 6.89 (s, 1H), 6.48 (s, 1H), 6.19 (t, J=5.8 Hz, 1H), 6.16 (dd, J=7.3, 1.9 Hz, 1H), 4.59 (d, J=5.8 Hz, 2H), 2.96-2.87 (m, 2H), 2.84-2.75 (m, 2H), 2.54 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 162.9, 160.7, 154.3, 140.1, 139.54, 139.5, 137.9, 133.2, 128.7, 128.6, 128.3, 127.8, 127.6, 127.2, 126.4, 121.8, 119.2, 109.3, 43.9, 36.9, 35.1, 15.9; MS (ES+) m/z 429.3 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. customwas partitioned between ethyl acetate (75 mL) and water (35 mL)
  3. washThe organic layer was washed sequentially with 10% aqueous hydrochloric acid (30 mL), saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (30 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with 20% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-8df4c906d00842df8cd882f149c962a7
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Reaction notes

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