Cesium carbonate → HCID 24951937, compound

HRID 600526Notes

Reaction equation

HRID 600526 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].Br[C:27]1[CH:28]=[CH:29][C:30]([C:33]([N:35]([CH3:37])[CH3:36])=[O:34])=[N:31][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[CH3:36][N:35]([CH3:37])[C:33]([C:30]1[CH:29]=[CH:28][C:27]([O:1][C:2]2[CH:3]=[C:4]([C:5](=[O:6])[NH:7][C:8]3[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=3)[CH:15]=[C:16]([O:18][C@H:19]3[CH2:23][CH2:22][N:21]([CH3:24])[C:20]3=[O:25])[CH:17]=2)=[CH:32][N:31]=1)=[O:34]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 228316185-bromo-N,N-dimethylpicolinamideHCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Product 1

HCID 24951937HCID 24951937, compoundYield 23%

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), 5-bromo-N,N-dimethyl-pyridine-2-carboxamide (CAS no. 845305-86-4) (165 mg, 0.72 mmol), cesium carbonate (587 mg, 1.8 mmol) and tris(triphenylphosphine)copper bromide (CAS no. 15709-74-7) (112 mg, 0.12 mmol) in N,N-dimethylacetamide (5 mL) was stirred at 160° C. for 6 hours. The N,N-dimethylacetamide was evaporated under reduced pressure and the residue was dissolved in water (20 mL) extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica eluting with 0-5% methanol in DCM. The resulting compound was dissolved in ethyl acetate (110 mL), washed with citric acid (1N, 10 mL), water (10 mL) and brine (10 mL), dried (MgSO4) and the solvent evaporated to afford the product (67 mg, 23%). 1H NMR δ (300 MHz, CDCl3) 2.14-2.26 (m, 1H), 2.52-2.67 (m, 1H), 2.55 (s, 3H), 2.94 (s, 3H), 3.15 (s, 6H), 3.34-3.57 (m, 2H), 4.94 (t, 1H), 6.97 (s, 1H), 7.23 (s, 1H), 7.40 (d, 1H), 7.46 (s, 1H), 7.72 (s, 1H), 8.14 (s, 1H), 8.38 (s, 1H), 8.58 (s, 1H), 9.52 (s, 1H); m/z 491 (M+H+).

Workup

  1. customThe N,N-dimethylacetamide was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in water (20 mL)
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by flash chromatography on silica eluting with 0-5% methanol in DCM
  7. dissolutionThe resulting compound was dissolved in ethyl acetate (110 mL)
  8. washwashed with citric acid (1N, 10 mL), water (10 mL) and brine (10 mL)
  9. dry with materialdried (MgSO4)
  10. customthe solvent evaporated

Sources & evidence

ORD record
ord-107579f7dddc4781bcee1c9fac862ecc
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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