Dimethylformamide → 3-cyano-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide

HRID 2261881Notes

Reaction equation

HRID 2261881 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([N:20]([CH3:25])[S:21]([CH3:24])(=[O:23])=[O:22])[CH:19]=1)[C:5]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)[CH3:9])=[O:6].[CH3:26][N:27](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:26]([C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([N:20]([CH3:25])[S:21]([CH3:24])(=[O:23])=[O:22])[CH:19]=1)[C:5]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)[CH3:9])=[O:6])#[N:27]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 589900843-bromo-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide2×

Product 1

HCID 589901463-cyano-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a solution of 3-bromo-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide (Intermediate X) (0.033 g, 0.077 mmol) in 0.80 mL degassed DMF (degassed by bubbling a stream of argon through solvent for 5 min) was added Zn(CN)2 (0.011 g, 0.092 mmol) and Pd(PPh3)4 (0.009 g, 0.008 mmol). The reaction vessel was purged thoroughly with argon, then sealed and microwaved at 180° C. for 30 min. The reaction was diluted with EtOAc, and the organics were washed with 3M aqueous LiCl. The aqueous washed with fresh EtOAc (2×), the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (5->75% EtOAc/hexanes) to afford 3-cyano-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide as a white foam. 1H NMR (CDCl3, 400 MHz) δ 8.04 (t, J=2.0 Hz, 1H), 7.91 (t, J=1.3 Hz, 1H), 7.78 (t, J=1.5 Hz, 1H), 7.36-7.7.31 (m, 2H), 7.05-7.00 (m, 2H), 6.67 (d, J=7.5 Hz, 1H), 5.25 (q, J=7.1 Hz, 1H), 3.34 (s, 3H), 2.87 (s, 3H), 1.59 (d, J=7.0 Hz, 3H). LCMS [M+H]+=376.

Workup

  1. customdegassed
  2. customby bubbling a stream of argon through solvent for 5 min)
  3. customThe reaction vessel was purged thoroughly with argon
  4. customsealed
  5. custommicrowaved at 180° C. for 30 min
  6. additionThe reaction was diluted with EtOAc
  7. washthe organics were washed with 3M aqueous LiCl
  8. washThe aqueous washed with fresh EtOAc (2×)
  9. washthe combined organics were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel chromatography (5->75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1ffb2a1e66dd448b8a4609a1d7fb9b28
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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