Ethyl Acetate → Methyl 4-(3-{[(3-Methoxy-5-Methylpyrazin-2-yl)[(2-Methylpropoxy)carbonyl]aMino]sulfonyl}pyridin-2-yl)benzoate

HRID 1384228Notes

Reaction equation

HRID 1384228 reaction equation
[F-].[K+].Cl[C:4]1[C:9]([S:10]([N:13]([C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])[C:14]2[C:19]([O:20][CH3:21])=[N:18][C:17]([CH3:22])=[CH:16][N:15]=2)(=[O:12])=[O:11])=[CH:8][CH:7]=[CH:6][N:5]=1.[CH3:30][O:31][C:32]([C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)=[O:33].C(OCC)(=O)C>O.C1(C)C=CC=CC=1.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>[CH2:26]([O:25][C:23]([N:13]([C:14]1[C:19]([O:20][CH3:21])=[N:18][C:17]([CH3:22])=[CH:16][N:15]=1)[S:10]([C:9]1[C:4]([C:37]2[CH:38]=[CH:39][C:34]([C:32]([O:31][CH3:30])=[O:33])=[CH:35][CH:36]=2)=[N:5][CH:6]=[CH:7][CH:8]=1)(=[O:12])=[O:11])=[O:24])[CH:27]([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 27343694-Methoxycarbonylphenylboronic acidHCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamate

Product 1

HCID 22325614Methyl 4-(3-{[(3-Methoxy-5-Methylpyrazin-2-yl)[(2-Methylpropoxy)carbonyl]aMino]sulfonyl}pyridin-2-yl)benzoateYield 82.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of potassium fluoride (7.0 g) in water (150 ml) was added to a solution of 2-chloro-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (8.3 g), 4-methoxycarbonylphenylboronic acid (7.9 g) and tetrakis(triphenylphosphine)palladium(0) (1.0 g) in toluene (150 ml) and the mixture was heated under reflux under argon for 18 hours. Ethyl acetate (150 ml) was added and the organic phase was separated. The solution was washed with 2M sodium hydroxide solution (100 ml) and water (250 ml) and then dried (MgSO4). Volatile material was removed by evaporation and the residue was triturated with ethyl acetate/hexane (1:3 v/v) to give N-(isobutoxycarbonyl)-2-(4-methoxycarbonylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (8.5 g), m.p. 134-136° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux under argon for 18 hours
  3. customthe organic phase was separated
  4. washThe solution was washed with 2M sodium hydroxide solution (100 ml) and water (250 ml)
  5. dry with materialdried (MgSO4)
  6. customVolatile material was removed by evaporation
  7. customthe residue was triturated with ethyl acetate/hexane (1:3 v/v)

Sources & evidence

ORD record
ord-57bc4239c27f441d9019406fc55826b4
Source dataset
uspto-grants-2001_07
Patent number
US06258817B1

Reaction notes

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