Réaction #1015781

Équation de réaction

Ethanol

sodium triacetoxyborohydride

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one

cyclobutylamine

→

8-(5-bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-8-azabicyclo[3.2.1]octan-3-amine

Rendement 89.6%

Solvants

toluene

Conditions de réaction

Traitement

1. 1
   Températureheated
2. 2
   Températureto reflux for 2 h
3. 3
   workup.STIRRINGthe reaction stirred
4. 4
   ConcentrationThe reaction was then concentrated in vacuum to a gum
5. 5
   workup.ADDITIONdiluted with ethyl acetate (100 mL) and saturated sodium hydrogen carbonate solution (50 mL)
6. 6
   workup.STIRRINGshaken
7. 7
   AutreThe ethyl acetate layer was then separated
8. 8
   Séchagedried over sodium sulphate
9. 9
   Concentrationconcentrated in vacuum

Mode opératoire

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one (1.5 g, 4.43 mmol) in toluene (60 mL) was treated with cyclobutylamine (3.145 g, 44.3 mmol) and heated with stirring to reflux for 2 h. Ethanol (100 mL) and sodium triacetoxyborohydride (9.347 g, 44.3 mmol) were added and the reaction stirred and warmed at 30° C. over 3 days. The reaction was then concentrated in vacuum to a gum, diluted with ethyl acetate (100 mL) and saturated sodium hydrogen carbonate solution (50 mL) and shaken. The ethyl acetate layer was then separated, dried over sodium sulphate and concentrated in vacuum to give 8-(5-bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-8-azabicyclo[3.2.1]octan-3-amine as a yellow solid (1.799 g, 3.97 mmol, 89%). 1H NMR (CDCl3) δ: 1.5 (3H, d, J=12 Hz), 1.65 (3H, br s), 1.93 (2H, br s), 2.1 (2H, d, J=6 Hz), 2.22 (2H, m), 2.4 (2H, m), 3.0 (1H, br s), 3.3 (1H, m), 4.63 (2H, br s), 7.3 (1H, s), 8.45 (1H, s).

Source