Sodium hydride → 4-[(4-But-2-ynyloxy-benzenesulfonyl)-methyl-amino]-3-methyl-isoxazolo[5,4-b]pyridine-5-carboxylic acid ethyl ester

HRID 496578Notes

Reaction equation

HRID 496578 reaction equation
[H-].[Na+].[CH2:3]([O:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=1)[C:4]#[C:5][CH3:6].[CH2:19]([O:21][C:22]([C:24]1[C:25](Cl)=[C:26]2[C:32]([CH3:33])=[N:31][O:30][C:27]2=[N:28][CH:29]=1)=[O:23])[CH3:20]>CN1CCCC1=O>[CH2:19]([O:21][C:22]([C:24]1[C:25]([N:17]([S:14]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH2:3][C:4]#[C:5][CH3:6])=[CH:9][CH:10]=2)(=[O:15])=[O:16])[CH3:18])=[C:26]2[C:32]([CH3:33])=[N:31][O:30][C:27]2=[N:28][CH:29]=1)=[O:23])[CH3:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10847662Ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylateHCID 111607834-But-2-ynyloxy-N-methyl-benzenesulfonamide

Product 1

HCID 697336794-[(4-But-2-ynyloxy-benzenesulfonyl)-methyl-amino]-3-methyl-isoxazolo[5,4-b]pyridine-5-carboxylic acid ethyl esterYield 90.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a suspension of 0.105 g (0.63 mmol) of 60% sodium hydride in 8 mL of 1-methyl-2-pyrrolidinone was added 0.628 g (2.63 mmol) of the product of Example 5 and the resulting mixture was stirred for 30 minutes at room temperature. A solution of 0.601 g (2.50 mmol) of ethyl-4-chloro-3-methylisoxazolo[5,4-b]pyridine-5-carboxylate in 7 mL of 1-methyl-2-pyrrolidinone was added and the reaction was heated to 80-90° C. for 48 h. The reaction mixture was then concentrated in vacuo and the residue was diluted with dichloromethane. The organics were washed with water, 2N citric acid solution and brine, dried over Na2SO4, filtered through Magnesol® and concentrated in vacuo. The residue was triturated with ethyl acetate/hexanes and the resulting solid was filtered and dried in vacuo to provide 1.0 g (90%) of the product as a solid; m.p.85-90° C. Electrospray Mass Spec: 444 (M+H)+.

Workup

  1. temperaturethe reaction was heated to 80-90° C. for 48 h
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. additionthe residue was diluted with dichloromethane
  4. washThe organics were washed with water, 2N citric acid solution and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered through Magnesol®
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with ethyl acetate/hexanes
  9. filtrationthe resulting solid was filtered
  10. customdried in vacuo

Sources & evidence

ORD record
ord-1843f4612dbe48459ec792811be30911
Source dataset
uspto-grants-2005_09
Patent number
US06946473B2

Reaction notes

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