Carbonate Ion → Methyl 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate

HRID 600534Notes

Reaction equation

HRID 600534 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@H:13]2[CH2:17][CH2:16][N:15]([CH3:18])[C:14]2=[O:19])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[N:20]1([C:24]([C:26]2[CH:31]=[N:30][C:29](Cl)=[CH:28][N:27]=2)=[O:25])[CH2:23][CH2:22][CH2:21]1.C(=O)([O-])[O-]>CC(N(C)C)=O>[N:20]1([C:24]([C:26]2[N:27]=[CH:28][C:29]([O:1][C:2]3[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@H:13]4[CH2:17][CH2:16][N:15]([CH3:18])[C:14]4=[O:19])[CH:11]=3)[C:5]([O:7][CH3:8])=[O:6])=[N:30][CH:31]=2)=[O:25])[CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 19660Carbonate IonHCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanone2×HCID 59761136methyl 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate2×

Product 1

HCID 59761154Methyl 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoateYield 71.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate (Intermediate 8) (265 mg, 1.0 mmol), azetidin-1-yl-(5-chloropyrazin-2-yl)methanone (Intermediate 32) (198 mg, 1.0 mmol) and polymer supported-carbonate (690 mg, 2.0 mmol) in DMA (5 mL) was stirred at 100° C. for 1 hr. The mixture was filtered and the DMA was removed under reduced pressure. The residue was dissolved in ethyl acetate (50 mL), washed with saturated sodium bicarbonate (10 mL), water (20 mL) and brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by chromatography on silica eluting with 20-100% ethyl acetate in isohexane then 10% Methanol in DCM to give afford the product (304 mg, 71%). 1H NMR δ (300 MHz, CDCl3) 2.13-2.27 (m, 1H), 2.31-2.44 (m, 2H), 2.53-2.66 (m, 1H), 2.94 (s, 3H), 3.35-3.58 (m, 2H), 3.90 (s, 3H), 4.26 (t, 2H), 4.68 (t, 2H), 4.93 (t, 1H), 7.14 (s, 1H), 7.46 (s, 1H), 7.60 (s, 1H), 8.31 (s, 1H), 8.84 (s, 1H); m/z 427 (M+H)+

Workup

  1. filtrationThe mixture was filtered
  2. customthe DMA was removed under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  4. washwashed with saturated sodium bicarbonate (10 mL), water (20 mL) and brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe residue was purified by chromatography on silica eluting with 20-100% ethyl acetate in isohexane
  9. custom10% Methanol in DCM to give

Sources & evidence

ORD record
ord-f79ff416f8b445f9989722ff5731a944
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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