Toluene → HCID 21186306, compound

HRID 361470Notes

Reaction equation

HRID 361470 reaction equation
[C:1]([C:4](C)([CH3:15])[CH2:5]OB(C1C=CC=CC=1)O)([OH:3])=[O:2].Cl[C:18]1[C:23]([S:24]([N:27]([C:37]([O:39][CH2:40][CH:41]([CH3:43])[CH3:42])=[O:38])[C:28]2[C:33]([O:34][CH3:35])=[N:32][C:31]([CH3:36])=[CH:30][N:29]=2)(=[O:26])=[O:25])=[CH:22][CH:21]=[CH:20][N:19]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:50]1([CH3:56])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>O>[C:1]([C:4]([CH3:15])([CH3:5])[CH2:56][C:50]1[CH:55]=[CH:54][C:53]([C:18]2[C:23]([S:24]([N:27]([C:37]([O:39][CH2:40][CH:41]([CH3:43])[CH3:42])=[O:38])[C:28]3[C:33]([O:34][CH3:35])=[N:32][C:31]([CH3:36])=[CH:30][N:29]=3)(=[O:26])=[O:25])=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:52][CH:51]=1)([OH:3])=[O:2]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 11015197Isobutyl (2-chloropyridin-3-yl)sulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamateHCID 70066777HCID 70066777, compound

Product 1

HCID 21186306HCID 21186306, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

(2-Carboxy-2-methylpropyl)phenylboronic acid (608 mg), 2-chloro-N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (1.03 g) and sodium carbonate (583 mg) were added to a mixture of toluene (25 ml) ethanol (25 ml) and water (10 ml). The mixture was deoxygenated by alternatively bubbling argon through and evacuating (3 cycles) and tetrakis(triphenylphosphine)palladium(0) (100 mgs) was added. The reaction mixture was heated to 85° C. for 18 hours, cooled to ambient temperature and partitioned between water (15 ml) and ethyl acetate (25 ml). The organic phase was extracted with saturated aqueous sodium carbonate solution (15 ml) and the combined aqueous phases were washed with ethyl acetate (15 ml). The aqueous phase was acidified with 2M hydrochloric acid to pH 1 and extracted with ethyl acetate (3×30 ml). The combined organic extracts were dried (MgSO4) and evaporated to give 2-[4-(2-carboxy-2-methylpropyl)phenyl]-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (495 mg); 1H NMR (d6 -DMSO): 0.6 (d, 6 H), 1.10 (s, 6 H), 1.51-1.69 (m, 1 H), 2.52 (s-partly obscured by DMSO), 2.87 (s, 2 H), 3.82 (d, 2 H), 3.95 (s, 3 H), 7.20 (d, 2 H), 7.43 (d, 2 H), 7.79 (dd, 1 H), 8.16 (s, 1 H), 8.84-8.97 (m, 2 H); mass spectum (+ve ESP) 557.2 (M+H)+.

Workup

  1. customThe mixture was deoxygenated by alternatively bubbling argon through and
  2. customevacuating (3 cycles) and tetrakis(triphenylphosphine)palladium(0) (100 mgs)
  3. additionwas added
  4. temperaturecooled to ambient temperature
  5. custompartitioned between water (15 ml) and ethyl acetate (25 ml)
  6. extractionThe organic phase was extracted with saturated aqueous sodium carbonate solution (15 ml)
  7. washthe combined aqueous phases were washed with ethyl acetate (15 ml)
  8. extractionextracted with ethyl acetate (3×30 ml)
  9. dry with materialThe combined organic extracts were dried (MgSO4)
  10. customevaporated

Sources & evidence

ORD record
ord-57b755c51b2949c0b5b37faa126ec9ef
Source dataset
uspto-grants-1999_02
Patent number
US05866568

Reaction notes

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