Hydrochloric Acid → ZD 2574

HRID 361410Notes

Reaction equation

HRID 361410 reaction equation
[OH-].[Na+].C(OC([N:10]([C:30]1[C:35]([O:36][CH3:37])=[N:34][C:33]([CH3:38])=[CH:32][N:31]=1)[S:11]([C:14]1[C:15]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH:27]([CH3:29])[CH3:28])=[CH:22][CH:21]=2)=[N:16][CH:17]=[CH:18][CH:19]=1)(=[O:13])=[O:12])=O)C(C)C.O.Cl>CO>[CH2:26]([C:23]1[CH:22]=[CH:21][C:20]([C:15]2[C:14]([S:11]([NH:10][C:30]3[C:35]([O:36][CH3:37])=[N:34][C:33]([CH3:38])=[CH:32][N:31]=3)(=[O:13])=[O:12])=[CH:19][CH:18]=[CH:17][N:16]=2)=[CH:25][CH:24]=1)[CH:27]([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 21186239HCID 21186239, compound

Product 1

HCID 9822972ZD 2574Yield 34.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1M sodium hydroxide solution (11.2 ml) was added to a solution of N-(isobutoxycarbonyl)-2-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (2.6 g) in methanol (50 ml) and the mixture was stirred and heated under reflux for 30 minutes. Water (100 ml) was added and the mixture was acidified to pH 3 with 2M hydrochloric acid. This mixture was extracted with ethyl acetate (5×30 ml) and the extracts were washed with water (30 ml) and saturated sodium chloride solution and dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by gradient elution with 0-15% ethyl acetate/hexane through a silica gel Mega Bond Elut column followed by trituration with ether to give 2-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (720 mg) as a solid, m.p. 128°-129° C.; 1H NMR (CDCl3): 0.95 (d, 6 H), 1.9 (m, 1 H), 2.3 (s, 3 H), 2.55 (d, 2 H), 3.8 (s, 3 H), 6.6 (s, 1 H), 7.1-7.3 (m, 4 H), 7.35 (s, 1 H), 7.5 (dd, 1 H), 8.7 (dd, 1 H), 8.8 (dd, 1 H); mass spectrum (positive electrospray (+ve ESP)): 413 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 30 minutes
  3. extractionThis mixture was extracted with ethyl acetate (5×30 ml)
  4. washthe extracts were washed with water (30 ml) and saturated sodium chloride solution
  5. dry with materialdried (MgSO4)
  6. customVolatile material was removed by evaporation
  7. customthe residue was purified by gradient elution with 0-15% ethyl acetate/hexane through a silica gel Mega Bond Elut column

Sources & evidence

ORD record
ord-3117b76a68b64d45afb8f4368da0501f
Source dataset
uspto-grants-1999_02
Patent number
US05866568

Reaction notes

Loading…