Sodium hydride → N-(4-chloro-3-methyl-5-isoxazolyl)-2-ethylthieno[2,3-b]-pyridine-3-sulfonamide

HRID 849505Notes

Reaction equation

HRID 849505 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:5]([CH3:10])=[N:6][O:7][C:8]=1[NH2:9].[CH2:11]([C:13]1[S:21][C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[C:14]=1[S:22](Cl)(=[O:24])=[O:23])[CH3:12]>C1COCC1>[Cl:3][C:4]1[C:5]([CH3:10])=[N:6][O:7][C:8]=1[NH:9][S:22]([C:14]1[C:15]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[S:21][C:13]=1[CH2:11][CH3:12])(=[O:24])=[O:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 105828224-Chloro-3-methyl-1,2-oxazol-5-amineHCID 120449152-Ethylthieno[2,3-b]pyridine-3-sulfonyl chloride

Product 1

HCID 15435829N-(4-chloro-3-methyl-5-isoxazolyl)-2-ethylthieno[2,3-b]-pyridine-3-sulfonamideYield 79.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of NaH (38 mg, 1.6 mmoles) in THF (5 ml) at ambient temperature was added 4-chloro-3-methyl-5-amino isoxazole (84 mg, 0.63 mmoles). The mixture was stirred 1 hr. at ambient temperature then cooled to 0° C. followed by the addition of 2-ethylthieno[2,3-b]pyridine-3-sulfonyl chloride (0.19 g, 0.73 mmoles) via cannula in THF (2 ml). The cooling bath was removed and the brown mixture was stirred 1 hr. at ambient temperature and then diluted with 3% NaOH (50 ml) and washed with CHCl3 (2×75 ml). The aqueous layer was acidified to pH 4 using concentrated HCl, upon which a precipitate formed. The aqueous phase was extracted with EtOAc (50 ml), and the organic layer was dried (MgSO4), filtered and concentrated to collect 0.23 g of a yellow oil. Recrystallization from EtOAc/hexanes provided 0.18 g (79%) of the title compound as a light yellow solid, m.p. 152-154° C.

Workup

  1. customThe cooling bath was removed
  2. stirringthe brown mixture was stirred 1 hr
  3. additionat ambient temperature and then diluted with 3% NaOH (50 ml)
  4. washwashed with CHCl3 (2×75 ml)
  5. customupon which a precipitate formed
  6. extractionThe aqueous phase was extracted with EtOAc (50 ml)
  7. dry with materialthe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto collect 0.23 g of a yellow oil
  11. customRecrystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-380686f7bc544ea48e254bf92aa27ffe
Source dataset
uspto-grants-2000_01
Patent number
US06013655

Reaction notes

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