Potassium Carbonate → 3-[2-Chloro-4-(dimethylcarbamoyl)phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide

HRID 600524Notes

Reaction equation

HRID 600524 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].[Cl:26][C:27]1[CH:28]=[C:29]([CH:35]=[CH:36][C:37]=1F)[C:30]([N:32]([CH3:34])[CH3:33])=[O:31].C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C>[Cl:26][C:27]1[CH:28]=[C:29]([C:30](=[O:31])[N:32]([CH3:33])[CH3:34])[CH:35]=[CH:36][C:37]=1[O: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]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 593468623-Chloro-4-fluoro-n,n-dimethylbenzamideHCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Product 1

HCID 249537153-[2-Chloro-4-(dimethylcarbamoyl)phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamideYield 31%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (206 mg, 0.6 mmol), 3-chloro-4-fluoro-N,N-dimethyl-benzamide (CAS no. 871657-07-7) (192 mg, 0.9 mmol) and potassium carbonate (166 mg, 1.2 mmol) in N,N-dimethylacetamide (5 mL) was stirred at 160° C. for 6 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL), washed with water (2×20 mL) and brine (10 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 0-4% methanol in DCM to afford the product (98 mg, 31%). 1H NMR δ (300 MHz, CDCl3) 2.10-2.27 (m, 1H), 2.54-2.67 (m, 1H), 2.55 (s, 3H), 2.93 (s, 3H), 2.98-3.19 (m, 6H), 3.34-3.57 (m, 2H), 4.92 (t, 1H), 6.86 (s, 1H), 7.06 (d, 1H), 7.16 (s, 1H), 7.33 (d, 1H), 7.40 (s, 1H), 7.57 (s, 1H), 8.13 (s, 1H), 8.53 (s, 1H), 9.51 (s, 1H); m/z 524 (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) and brine (10 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 eluting with 0-4% methanol in DCM

Sources & evidence

ORD record
ord-05028119f3484374bc602f5014434235
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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