Toluene → 4-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]pyridine-3-sulphonamide

HRID 1107468Notes

Reaction equation

HRID 1107468 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[S:8]([N:11]([C:20]1[C:25]([O:26][CH3:27])=[N:24][C:23]([CH3:28])=[CH:22][N:21]=1)[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])(=[O:10])=[O:9].[CH2:29]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)[CH:30]([CH3:32])[CH3:31].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOCC.C(O)C>[CH2:29]([C:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[S:8]([N:11]([C:20]2[C:25]([O:26][CH3:27])=[N:24][C:23]([CH3:28])=[CH:22][N:21]=2)[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])(=[O:10])=[O:9])=[CH:35][CH:34]=1)[CH:30]([CH3:32])[CH3:31]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2773472(4-Isobutylphenyl)boronic acidHCID 211862784-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]pyridine-3-sulphonamide

Product 1

HCID 211862384-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]pyridine-3-sulphonamideYield 77.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

Tetrakis(triphenylphosphine)palladium(0) (0.018 g) was added to a deoxygenated mixture of 4-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2(trimethylsilyl) ethoxymethyl]pyridine-3-sulphonamide (0.225 g), 4-isobutylphenylboronic acid (0.109 g), toluene (4 ml), ethanol (2 ml) and 2M sodium carbonate solution (6 ml) and the mixture was stirred and heated under reflux for 18 hours. Ether (25 ml) was added and the mixture was washed with water (2×25 ml) and saturated sodium chloride solution. Aqueous layers were back-extracted with ether (25 ml). The organic extracts were combined and dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by gradient elution with 25-50% ethyl acetate/hexane through a silica gel Mega Bond Elut column to give 4-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]-pyridine-3-sulphonamide (0.213 g) as an oil; 1H NMR (d6 -DMSO): -0.1 (s, 9H), 0.7 (t, 2H), 0.9 (d, 6H), 1.9 (m, 1H), 2.45 (s, 3H), 2.5 (d, 2H), 3.5 (t, 2H), 3.8 (s, 2H), 7.2 (d, 2H), 7.3 (d, 2H), 7.4 (d, 1H), 8.0 (s, 1H), 8.8 (d, 1H), 9.2 (s, 1H); mass spectrum (+ve ESP): 543 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 18 hours
  3. washthe mixture was washed with water (2×25 ml) and saturated sodium chloride solution
  4. extractionAqueous layers were back-extracted with ether (25 ml)
  5. dry with materialdried (MgSO4)
  6. customVolatile material was removed by evaporation
  7. customthe residue was purified by gradient elution with 25-50% ethyl acetate/hexane through a silica gel Mega Bond Elut column

Sources & evidence

ORD record
ord-7e70689e6165426884b8918420586f3f
Source dataset
uspto-grants-2000_05
Patent number
US06060475

Reaction notes

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