Acetic Acid → HCID 21186232, compound

HRID 1384240Notes

Reaction equation

HRID 1384240 reaction equation
C(O)(=O)C.C[O:6][C:7]([CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:22]([S:23]([N:26](C(OCC(C)C)=O)[C:27]3[C:32]([O:33][CH3:34])=[N:31][C:30]([CH3:35])=[CH:29][N:28]=3)(=[O:25])=[O:24])=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:13][CH:12]=1)=[O:8].N(C([O-])=O)=NC([O-])=O.[K+].[K+]>C(COC)OC>[C:7]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:22]([S:23]([NH:26][C:27]3[C:32]([O:33][CH3:34])=[N:31][C:30]([CH3:35])=[CH:29][N:28]=3)(=[O:24])=[O:25])=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:13][CH:12]=1)([OH:8])=[O:6]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6096233Potassium diazene-1,2-dicarboxylateHCID 54341699HCID 54341699, compound

Product 1

HCID 21186232HCID 21186232, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
45 °C

Procedure

A 1M solution of acetic acid in dimethoxyethane (5.6 ml) was added dropwise over 3 hours to a mixture of 2-[4-(2-[methoxycarbonyl]vinyl)phenyl]-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (250 mg) and potassium azodicarboxylate (1.4 g) in dry dimethoxyethane (20 ml) at 45° C. The mixture was heated at 45° C. for 18 hours. Insoluble material was removed by filtration and the filtrate was concentrated. The residue was eluted through a pad of silica gel with ethyl acetate/hexane (1:3 v/v) and the resulting solid (230 mg) was dissolved in a mixture of tetrahydrofuran (16 ml) and methanol (4 ml). A solution of lithium hydroxide (118 mg) in water (4 ml) was added and the solution was stirred for 18 hours. Volatile material was removed by evaporation and the residue was dissolved in water (15 ml). The solution was washed with ethyl acetate (2×15 ml) and acidified with 20% aqueous citric acid. The mixture was extracted with ethyl acetate (2×15 ml) and the extracts were washed with water (10 ml) and saturated sodium chloride solution (50 ml) and dried (MgSO4). Volatile material was removed by evaporation and the residue was triturated with ether to give 2-[4-(2-carboxyethyl)phenyl]-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (42 mg), m.p. 166-168° C.; 1H NMR (CDCl3): 2.25 (s, 3H), 2.6 (t, 2H), 3.0 (t, 2H), 3.8 (s, 3H), 7.2-7.3 (m, 5H), 7.45-7.55 (m, 1H), 8.65 (d, 1H), 8.8 (d, 1H), 10.25-10.5 (br, 1H).

Workup

  1. customInsoluble material was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. washThe residue was eluted through a pad of silica gel with ethyl acetate/hexane (1:3 v/v)
  4. dissolutionthe resulting solid (230 mg) was dissolved in a mixture of tetrahydrofuran (16 ml) and methanol (4 ml)
  5. additionA solution of lithium hydroxide (118 mg) in water (4 ml) was added
  6. customVolatile material was removed by evaporation
  7. dissolutionthe residue was dissolved in water (15 ml)
  8. washThe solution was washed with ethyl acetate (2×15 ml)
  9. extractionThe mixture was extracted with ethyl acetate (2×15 ml)
  10. washthe extracts were washed with water (10 ml) and saturated sodium chloride solution (50 ml)
  11. dry with materialdried (MgSO4)
  12. customVolatile material was removed by evaporation
  13. customthe residue was triturated with ether

Sources & evidence

ORD record
ord-0a2a26070dae4300973afd8cd8c303c6
Source dataset
uspto-grants-2001_07
Patent number
US06258817B1

Reaction notes

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