Ethanol → HCID 21186252, compound

HRID 361463Notes

Reaction equation

HRID 361463 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([CH:10]([CH3:21])[CH2:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)([OH:9])=[O:8].Cl[C:23]1[C:28]([S:29]([N:32]([C:42]([O:44][CH2:45][CH:46]([CH3:48])[CH3:47])=[O:43])[C:33]2[C:38]([O:39][CH3:40])=[N:37][C:36]([CH3:41])=[CH:35][N:34]=2)(=[O:31])=[O:30])=[CH:27][CH:26]=[CH:25][N:24]=1.C(O)C>O.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.C1(C)C=CC=CC=1>[CH2:45]([O:44][C:42]([N:32]([C:33]1[C:38]([O:39][CH3:40])=[N:37][C:36]([CH3:41])=[CH:35][N:34]=1)[S:29]([C:28]1[C:23]([C:15]2[CH:16]=[CH:17][C:12]([CH2:11][CH:10]([C:7]([OH:9])=[O:8])[CH3:21])=[CH:13][CH:14]=2)=[N:24][CH:25]=[CH:26][CH:27]=1)(=[O:31])=[O:30])=[O:43])[CH:46]([CH3:48])[CH3:47]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamateHCID 21186218HCID 21186218, compound

Product 1

HCID 21186252HCID 21186252, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Tetrakis(triphenylphosphine)palladium (0) (500 mg) was added to a deoxygenated solution of sodium carbonate (3.74 g), 4-(2-carboxypropyl)phenyl boronic acid (3.67 g) and 2-chloro-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methyl-pyrazin-2-yl)pyridine-3-sulphonamide (6.1 g) in a mixture of water (30 ml), ethanol (75 ml) and toluene (75 ml). The mixture was stirred and heated under argon at 80° C. for 17 hours and then allowed to cool to ambient temperature. Ice water (5 g) was added and the reaction extracted with ethyl acetate (75 ml). The combined organic layers were extracted with saturated aqueous sodium carbonate solution (2×15 ml) and combined aqueous extracts were acidified to pH 2 with 2M hydrochloric-acid and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried (MgSO4) and evaporated to low volume affording crystalline material which was filtered and washed with diethyl ether to give N-(isobutoxycarbonyl)-2-(4-(2-carboxypropyl)phenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (3.11 g); NMR 1H (d6 -DMSO): 0.61 (d, 6 H), 1.09 (d, 3 H), 1.50-1.73 (m, 1 H), 2.55 (partly obscured by DMSO, 3 H), 2.6-2.77 (m, 2 H), 2.72-3.09 (m, 1 H), 2.83 (d, 2 H), 3.96 (s, 3 H), 7.25 (d, 2 H), 7.43 (d, 2 H), 7.78 (dd, 1 H), 8.15 (s, 1 H), 8.83-8.96 (m, 2 H), 12.14 (br s, 1 H); mass spectrum (-ve ESP) 541.1 (M-H )-.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionthe reaction extracted with ethyl acetate (75 ml)
  3. extractionThe combined organic layers were extracted with saturated aqueous sodium carbonate solution (2×15 ml)
  4. extractionextracted with ethyl acetate (3×100 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customevaporated to low volume
  7. customaffording crystalline material which
  8. filtrationwas filtered
  9. washwashed with diethyl ether

Sources & evidence

ORD record
ord-2d6153a3662d44299c6fb0fd6a8d2327
Source dataset
uspto-grants-1999_02
Patent number
US05866568

Reaction notes

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