Water → 2-(4-cyanophenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide

HRID 361451Notes

Reaction equation

HRID 361451 reaction equation
Cl[C:2]1[C:7]([S:8]([N:11]([C:21]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[O:22])[C:12]2[C:17]([O:18][CH3:19])=[N:16][C:15]([CH3:20])=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:28]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)#[N:29].[F-].[K+].O>C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:28]([C:30]1[CH:35]=[CH:34][C:33]([C:2]2[C:7]([S:8]([N:11]([C:21]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[O:22])[C:12]3[C:17]([O:18][CH3:19])=[N:16][C:15]([CH3:20])=[CH:14][N:13]=3)(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:32][CH:31]=1)#[N:29]

Participants

8

Reactant 4

HCID 962Water2×HCID 522689Potassium FluorideHCID 27343264-Cyanophenylboronic acidHCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamate

Product 1

HCID 211862212-(4-cyanophenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamideYield 82.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

A stirred mixture of 1,1'-bis(diphenylphosphino)ferrocene (0.532 g) and palladium (II) acetate (0.162 g) in deoxygenated toluene (95 ml) was heated at 50° C. under argon for 30 minutes then cooled to ambient temperature. 2-Chloro-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (10 g), 4-cyanophenylboronic acid (8.47 g), potassium fluoride (8.37 g) and water (95 ml) were added and the resultant mixture was stirred and heated under reflux for 8 hours then cooled. Water (100 ml) was added and the mixture was extracted with ethyl acetate (100 ml) then filtered through diatomaceous earth. The aqueous layer was separated and extracted further with ethyl acetate (2×100 ml). The organic extracts were combined, washed with aqueous sodium carbonate (100 ml of a 2M solution) and water (100 ml) then treated with charcoal and dried (MgSO4). Volatile material was removed by evaporation and the residue was recrystallised from ether/isohexane to give 2-(4-cyanophenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (9.58 g) as a solid, 1H NMR (DMSO-d6): 0.6 (d, 6 H), 1.6 (m, 1 H), 2.6 (s, 3 H), 3.8 (d, 2 H), 4.0 (s, 3 H), 7.7 (d, 2 H), 7.9 (m, 3 H), 8.2 (s, 1 H), 8.9 (d, 1 H), 9.0 (d, 1 H); mass spectrum (+ve ESP): 482 (M+H)+.

Workup

  1. temperaturethen cooled to ambient temperature
  2. temperatureheated
  3. temperatureunder reflux for 8 hours
  4. temperaturethen cooled
  5. extractionthe mixture was extracted with ethyl acetate (100 ml)
  6. filtrationthen filtered through diatomaceous earth
  7. customThe aqueous layer was separated
  8. extractionextracted further with ethyl acetate (2×100 ml)
  9. washwashed with aqueous sodium carbonate (100 ml of a 2M solution) and water (100 ml)
  10. additionthen treated with charcoal
  11. dry with materialdried (MgSO4)
  12. customVolatile material was removed by evaporation
  13. customthe residue was recrystallised from ether/isohexane

Sources & evidence

ORD record
ord-efd751ced07445b09a21ca08977dab26
Source dataset
uspto-grants-1999_02
Patent number
US05866568

Reaction notes

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