Reacción #172641

Ecuación de reacción

methyl 6-bromo-1H-indazole-4-carboxylate

NaH

Iodocyclopentane

→

methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture was stirred at 100° C. overnight
2. 2
   TemperaturaAfter cooling to RT
3. 3
   Otrothe reaction mixture was partitioned between water and ethyl acetate
4. 4
   LavadoThe organic phase was washed with water and brine
5. 5
   Secadodried over MgSO4
6. 6
   Filtraciónfiltered
7. 7
   Otroevaporated
8. 8
   workup.ADDITIONHexanes was added to the brown oil and it
9. 9
   Otrowas purified
10. 10
    OtroThe less polar product was evaporated
11. 11
    Otroto give an orange oil
12. 12
    Otrowas dried on hivac overnight
13. 13
    Otrowas collected as 807 mg (32%)

Procedimiento

Ice-cooled methyl 6-bromo-1H-indazole-4-carboxylate (2 g, 7.84 mmol) in 30 mL of DMF was treated with NaH (60%, 345 mg, 8.63 mmol) and the mixture was stirred for 1 hr at 0° C. Iodocyclopentane (2.31 g, 11.8 mmol) was then added and the mixture was stirred at 100° C. overnight. After cooling to RT, the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with water and brine, dried over MgSO4, filtered and evaporated. Hexanes was added to the brown oil and it was purified using silica gel chromatography (eluent: Hex/EtOAc, gradient 0 to 25%). The less polar product was evaporated to give an orange oil, and was dried on hivac overnight. The product was confirmed to be the alkylated 1-isomer as suggested by 2D HNMR, and was collected as 807 mg (32%). 1H NMR (400 MHz, DMSO-d6): δ 8.40 (s, 1H) 8.37 (s, 1H) 7.81 (d, J=1.52 Hz, 1H) 5.26 (quin, J=7.07 Hz, 1H) 3.95 (s, 3H) 2.08-2.17 (m, 2H) 1.93-2.01 (m, 2H) 1.82-1.92 (m, 2H) 1.64-1.73 (m, 2H); LCMS (ES+): m/z=323.3/325.3

Fuente