تفاعل #155551

معادلة التفاعل

3-bromo-5-(cyclopropyloxy)pyridine

cesium carbonate

water

di-tert-Butyl {(4aS,5R,7aS)-7a-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl}imidodicarbonate

→

title compound

(4aS,5R,7aS)-7a-(5-(5-cyclopropoxypyridin-3-yl)-2-fluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

المذيبات

NaHCO3

ethanol

1,2-dimethoxyethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe reaction mixture was cooled to room temperature
2. 2
   استخلاصextracted with EtOAc (×3)
3. 3
   تجفيفThe combined organic layers were dried (MgSO4)
4. 4
   ترشيحfiltered
5. 5
   تركيزconcentrated in vacuo
6. 6
   أخرىThe residue was purified
7. 7
   workup.DISSOLUTIONThe purified product was dissolved in DCM (2 mL)
8. 8
   workup.WAITAfter 1 hour
9. 9
   أخرىthe solvents were removed in vacuo
10. 10
    استخلاصextracted with DCM (×3)
11. 11
    تجفيفThe combined organic layers were dried (MgSO4)
12. 12
    ترشيحfiltered
13. 13
    تركيزconcentrated

الإجراء التجريبي

di-tert-Butyl {(4aS,5R,7aS)-7a-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl}imidodicarbonate (0.13 g, 0.22 mmol) was dissolved in 1,2-dimethoxyethane (1.5 mL), water (0.7 mL) and ethanol (0.5 mL) The resulting solution was heated to 100° C. and to it was added 3-bromo-5-(cyclopropyloxy)pyridine (0.28 g, 1.32 mmol), cesium carbonate (0.43 g, 1.32 mmol) and bis(triphenylphosphine)palladium (II) dichloride (0.046 g, 0.066 mmol) and the reaction was stirred at 100° C. After 1 hour, the reaction mixture was cooled to room temperature, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography gradient 0-60% EtOAc in hexane). The purified product was dissolved in DCM (2 mL) and trifluoroacetic acid (1 mL). After 1 hour, the solvents were removed in vacuo. The residue was basified with saturated aqueous NaHCO3 and extracted with DCM (×3). The combined organic layers were dried (MgSO4), filtered and concentrated to leave the title compound. (58 mg)

المصدر