تفاعل #74483

معادلة التفاعل

Sodium hydride

Intermediate 1

2-(2-Chloro-5-((3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxy methyl)-tetrahydro-2H-pyran-2-yl)phenyl)acetonitrile

compound 6

2-(2-Chloro-5-((3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)phenyl)acetonitrile

N,N-dimethylacetamide

3,6-dichloropyridazine

compound 22

(2S,3R,4R,5S,6R)-2-(4-Chloro-3-((5-(methylthio)-1,3,4-thiadiazol-2-yl)methyl)phenyl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol

→

title compound

2-(2-Chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)phenyl)(6-chloropyridazin-3-yl)methanone

ظروف التفاعل

المعالجة

1. 1
   أخرىThe ice bath was removed
2. 2
   workup.STIRRINGthe reaction mixture was stirred at room temperature for 3.5 h
3. 3
   workup.ADDITIONH2O2 (2.50 mL) was added to reaction mixture
4. 4
   workup.WAITleft
5. 5
   workup.STIRRINGstirring additional hour
6. 6
   درجة الحرارةwarm-up to room temperature
7. 7
   غسيلThe reaction solution was washed with 1N HCl solution, 1N NaOH solution and brine
8. 8
   أخرىThe organic layer was collected
9. 9
   أخرىevaporated under a vacuum
10. 10
    أخرىThe crude mixture was further purified by flash column chromatography (Biotage SP1™)

الإجراء التجريبي

Sodium hydride (593 mg; 14.8 mmol; 60% in mineral oil) was added to stirred solution of Intermediate 1 (compound 6, 5.00 g; 7.42 mmol) in 20 mL of N,N-dimethylacetamide (DME) at 0° C. under nitrogen gas. The reaction mixture was stirred for 30 min, and 3,6-dichloropyridazine (compound 22, 1.25 g; 8.16 mmol) was added in one portion. The ice bath was removed, and the reaction mixture was stirred at room temperature for 3.5 h. Cooled to 0° C., H2O2 (2.50 mL) was added to reaction mixture and left stirring additional hour warm-up to room temperature. The reaction solution was washed with 1N HCl solution, 1N NaOH solution and brine. The organic layer was collected, and evaporated under a vacuum. The crude mixture was further purified by flash column chromatography (Biotage SP1™) to obtain 3.10 g (4.00 mmol; 54%) of the title compound as orange oil.

المصدر