Potassium Carbonate → 3-[(3S)-1-Methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)-5-(4-methylsulfonylphenoxy)benzamide

HRID 600514Notes

Reaction equation

HRID 600514 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@H:19]2[CH2:23][CH2:22][N:21]([CH3:24])[C:20]2=[O:25])[CH:17]=1)[C:5]([NH:7][C:8]1[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].F[C:27]1[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[CH3:24][N:21]1[CH2:22][CH2:23][C@H:19]([O:18][C:16]2[CH:15]=[C:4]([CH:3]=[C:2]([O:1][C:27]3[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=3)[CH:17]=2)[C:5]([NH:7][C:8]2[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=2)=[O:6])[C:20]1=[O:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 679941-Fluoro-4-(methylsulphonyl)benzeneHCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Product 1

HCID 249523043-[(3S)-1-Methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)-5-(4-methylsulfonylphenoxy)benzamideYield 68%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (136 mg, 0.4 mmol), 1-fluoro-4-methylsulfonyl-benzene (105 mg, 0.6 mmol) and potassium carbonate (111 mg, 0.8 mmol) in DMA (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL), washed with water (2×20 mL), brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 0-4% methanol in DCM to afford product (135 mg, 68%). 1H NMR δ (300 MHz, CDCl3) 2.15-2.30 (m, 1H), 2.53-2.69 (m, 4H), 2.94 (s, 3H), 3.08 (s, 3H), 3.36-3.58 (m, 2H), 4.96 (t, 1H), 7.02 (s, 1H), 7.15 (d, 2H), 7.25 (s, 1H), 7.50 (s, 1H), 7.93 (d, 2H), 8.15 (s, 1H), 8.55 (s, 1H), 9.53 (s, 1H); m/z 497 (M+H)+.

Workup

  1. customThe solution was evaporated under reduced pressure
  2. dissolutionthe residue dissolved in ethyl acetate (40 mL)
  3. washwashed with water (2×20 mL), brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by flash chromatography on silica
  8. washeluting with a gradient of 0-4% methanol in DCM

Sources & evidence

ORD record
ord-efe0e3daadb447d889bd1a8454931a5e
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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