Toluene → 2-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide

HRID 1384258Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1384258
[CH:1]1([CH2:4][C:5]2[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=2)[CH2:3][CH2:2]1.Cl[C:15]1[C:20]([S:21]([N:24]([C:34]([O:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:35])[C:25]2[C:30]([O:31][CH3:32])=[N:29][C:28]([CH3:33])=[CH:27][N:26]=2)(=[O:23])=[O:22])=[CH:19][CH:18]=[CH:17][N:16]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C(O)C>[CH:1]1([CH2:4][C:5]2[CH:10]=[CH:9][C:8]([C:15]3[C:20]([S:21]([N:24]([C:34]([O:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[O:35])[C:25]4[C:30]([O:31][CH3:32])=[N:29][C:28]([CH3:33])=[CH:27][N:26]=4)(=[O:22])=[O:23])=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:7][CH:6]=2)[CH2:3][CH2:2]1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamateHCID 18754990[4-(Cyclopropylmethyl)phenyl]boronic acid

Produkt 1

HCID 211863262-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamideAusbeute 50,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

4-(cyclopropylmethyl)benzeneboronic acid (1.5 g), 2-chloro-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (2.99 g) and sodium carbonate (912 mg) were added to a mixture of toluene (66 ml), ethanol (33 ml) and water (24 ml). The mixture was deoxygenated by alternatively bubbling argon through and evacuating (3 cycles) and tetrakis(triphenylphosphine)palladium(0) (347 mgs) was added. The reaction mixture was heated to 80° C. for 18 hours with efficient stirring and, after cooling, ethyl acetate (50 ml) and water (30 ml) were added. The organic phase was separated and the aqueous layer extracted with ethyl acetate (2×30 ml). The combined organic phases were washed with brine (15 ml), dried (MgSO4) and evaporated. The residue was purified by chromatography on a Mega Bond Elut column, eluting with a gradient of ethyl acetate in hexane (0-100%) to give 2-(4-cyclopropylmethylphenyl)-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (1.85 g); 1H NMR (d6-DMSO): 0.25 (q, 2H), 0.54 (m, 2H), 1.03 (M, 1H), 1.64 (m, 1H), 2.55 (s, 3H), 2.60 (d, 2H), 3.83 (d, 2H), 3.98 (s, 3H), 7.33 (d, 2H), 7.46 (d, 2H), 7.77 (dd, 1H), 8.15 (s, 1H), 8.10-8.95 (m, 2H); mass spectrum (+ve ESP) 511 (M+H)+.

Aufarbeitung

  1. customThe mixture was deoxygenated by alternatively bubbling argon through and
  2. customevacuating (3 cycles) and tetrakis(triphenylphosphine)palladium(0) (347 mgs)
  3. additionwas added
  4. temperatureafter cooling
  5. additionethyl acetate (50 ml) and water (30 ml) were added
  6. customThe organic phase was separated
  7. extractionthe aqueous layer extracted with ethyl acetate (2×30 ml)
  8. washThe combined organic phases were washed with brine (15 ml)
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customThe residue was purified by chromatography on a Mega Bond Elut column
  12. washeluting with a gradient of ethyl acetate in hexane (0-100%)

Quellen und Nachweise

ORD-Eintrag
ord-a90071df29124e0d98321645dcaf0353
Quelldatensatz
uspto-grants-2001_07
Patentnummer
US06258817B1

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