Hydrochloric Acid → Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamate

HRID 361412Notes

Reaction equation

HRID 361412 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[C:6]([NH:12][C:13](=[O:19])[O:14][CH2:15][CH:16]([CH3:18])[CH3:17])=[N:7][CH:8]=[C:9]([CH3:11])[N:10]=1.[Cl:20][C:21]1[C:26]([S:27](Cl)(=[O:29])=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=1.Cl>O.CN(C=O)C>[Cl:20][C:21]1[C:26]([S:27]([N:12]([C:13]([O:14][CH2:15][CH:16]([CH3:17])[CH3:18])=[O:19])[C:6]2[C:5]([O:4][CH3:3])=[N:10][C:9]([CH3:11])=[CH:8][N:7]=2)(=[O:29])=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 102199682-Chloropyridine-3-sulfonyl chlorideHCID 10889995Isobutyl (3-methoxy-5-methylpyrazin-2-yl)carbamate

Product 1

HCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamateYield 43.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in oil; 0.083 g) was added to a stirred solution of isobutyl N-(3-methoxy-5-methylpyrazin-2-yl)-carbamate (0.451 g) in dry N,N-dimethylfonmamide (DMF; 8 ml) at 4° C. The mixture was stirred whilst warming to ambient temperature over I hour, was recooled to 4° C. and 2-chloropyridine-3-sulphonyl chloride (0.40 g) was added in portions over 2 minutes. The mixture was allowed to warm to ambient temperature and stirred a further 30 minutes. Water (40 ml) was added, followed by 1M hydrochloric acid to acidify. This mixture was extracted with ethyl acetate (4×15 ml) and the organic extracts were washed with water (10 ml) and saturated sodium chloride solution (10 ml) and then dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by gradient elution with 0-35% ethyl acetate/hexane through a silica gel Mega Bond Elut column and triturated with ether to give 2-chloro-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)-pyridine-3-sulphonamide (0.34 g) as a solid, m.p. 99°-101° C.; 1H NMR (CDCl3): 0.7 (d, 6 H), 1.7 (m, 1 H), 2.5 (s, 3 H), 3.8 (d, 2 H), 4.0 (s, 3 H), 7.45 (dd, 1 H), 7.9 (s, 1 H), 8.6 (dd, 1 H), 8.7 (dd, 1 H); mass spectrum (+ve ESP): 415 (M+H)+.

Workup

  1. customwas recooled to 4° C.
  2. temperatureto warm to ambient temperature
  3. stirringstirred a further 30 minutes
  4. extractionThis mixture was extracted with ethyl acetate (4×15 ml)
  5. washthe organic extracts were washed with water (10 ml) and saturated sodium chloride solution (10 ml)
  6. dry with materialdried (MgSO4)
  7. customVolatile material was removed by evaporation
  8. customthe residue was purified by gradient elution with 0-35% ethyl acetate/hexane through a silica gel Mega Bond Elut column
  9. customtriturated with ether

Sources & evidence

ORD record
ord-31850f1fb7c44a97bd1458f3dc47bbb5
Source dataset
uspto-grants-1999_02
Patent number
US05866568

Reaction notes

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