Sodium hydride → HCID 67067770, compound

HRID 1037287Notes

Reaction equation

HRID 1037287 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[C:15]([O:16][CH3:17])=[C:14]2[C:10]([CH:11]=[N:12][NH:13]2)=[CH:9][CH:8]=1)=[O:6].[CH3:18][N:19]([CH3:24])[S:20](Cl)(=[O:22])=[O:21]>C1COCC1>[CH3:3][O:4][C:5]([C:7]1[C:15]([O:16][CH3:17])=[C:14]2[C:10]([CH:11]=[N:12][N:13]2[S:20](=[O:22])(=[O:21])[N:19]([CH3:24])[CH3:18])=[CH:9][CH:8]=1)=[O:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 83372Dimethylsulphamoyl chlorideHCID 11846514HCID 11846514, compound

Product 1

HCID 67067770HCID 67067770, compoundYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (60% dispersion in mineral oil, 1.27 g, 31.66 mmol) was added to anhydrous THF (100 mL) with stirring under an atmosphere of nitrogen. After 5 min, a solution of 7-methoxy-1H-indazole-6-carboxylic acid methyl ester (5.44 g, 26.38 mmol, prepared as described in J. Med. Chem. 2006, 49, 4762-4766) in anhydrous THF (50 mL) was added dropwise over 15 min. After stirring for 30 min, a solution of dimethylsulfamoyl chloride (3.68 mL, 34.3 mmol) in anhydrous THF (20 mL) was added dropwise over 10 min. After stirring for 2 h, the reaction mixture was quenched by addition of water (50 mL) and transferred to a separating funnel using EtOAc. The organic layer was washed with water. The aqueous layers were combined and extracted using EtOAc. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 20% EtOAc in DCM) to afford the title compound as a yellow solid (6.23 g, 75%). 1H NMR (400 MHz, DMSO-d6): δ 8.98 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.33 (d, J=8.8 Hz, 1H), 4.29 (s, 3H), 3.85 (s, 3H), 2.97 (s, 6H).

Workup

  1. stirringAfter stirring for 30 min
  2. stirringAfter stirring for 2 h
  3. customthe reaction mixture was quenched by addition of water (50 mL)
  4. customtransferred to a separating funnel
  5. washThe organic layer was washed with water
  6. extractionextracted
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-05126eb330c547ab9695ce2dab1beaf9
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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