Cesium carbonate → 3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)-5-(6-methylsulfonylpyridin-3-yl)oxy-benzamide

HRID 600525Notes

Reaction equation

HRID 600525 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]([S:33]([CH3:36])(=[O:35])=[O:34])=[N:31][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[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]=[N: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 10796Cesium carbonateHCID 134334245-Bromo-2-methanesulfonylpyridineHCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Product 1

HCID 249519383-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)-5-(6-methylsulfonylpyridin-3-yl)oxy-benzamideYield 40%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (305 mg, 0.6 mmol), 5-bromo-2-methylsulfonyl-pyridine (CAS no. 98626-95-0) (142 mg, 0.6 mmol), cesium carbonate (390 mg, 1.2 mmol) and tris(triphenylphosphine)copper bromide (CAS no. 15709-74-7) (112 mg, 0.12 mmol) in N,N-dimethylacetamide (5 mL) was stirred in the microwave at 160° C. for 6 hours. N,N-Dimethylacetamide was removed by evaporation under reduced pressure. The residue was partitioned between ethyl acetate (30 mL) and water (50 mL). The organic phase was separated and the aqueous layer was acidified with hydrochloric acid (1N, 5 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography on silica eluting with 0-5% methanol in DCM to afford the product (120 mg, 40%). 1H NMR δ (300 MHz, CDCl3) 2.14-2.32 (m, 1H), 2.52-2.69 (m, 1H), 2.55 (s, 3H), 2.94 (s, 3H), 3.23 (s, 3H), 3.35-3.59 (m, 2H), 4.96 (t, 1H), 7.05 (s, 1H), 7.27 (s, 1H), 7.48 (d, 1H), 7.54 (s, 1H), 8.07 (d, 1H), 8.14 (s, 1H), 8.49 (s, 1H), 8.55 (s, 1H), 9.51 (s, 1H); m/z 498 (M+H+).

Workup

  1. customN,N-Dimethylacetamide was removed by evaporation under reduced pressure
  2. customThe residue was partitioned between ethyl acetate (30 mL) and water (50 mL)
  3. customThe organic phase was separated
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica eluting with 0-5% methanol in DCM

Sources & evidence

ORD record
ord-3800aabdfe52442d8ef82070eb8c4e57
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

Loading…