Reaktion #172641

Reaktionsgleichung

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

NaH

Iodocyclopentane

→

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

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred at 100° C. overnight
2. 2
   TemperaturAfter cooling to RT
3. 3
   Sonstigethe reaction mixture was partitioned between water and ethyl acetate
4. 4
   WaschenThe organic phase was washed with water and brine
5. 5
   Trocknendried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated
8. 8
   workup.ADDITIONHexanes was added to the brown oil and it
9. 9
   Sonstigewas purified
10. 10
    SonstigeThe less polar product was evaporated
11. 11
    Sonstigeto give an orange oil
12. 12
    Sonstigewas dried on hivac overnight
13. 13
    Sonstigewas collected as 807 mg (32%)

Vorschrift

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

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