반응 #1015782

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

formalin

→

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

수율 81.0%

용매

formic acid

반응 조건

후처리

1. 1
   농축The reaction was then concentrated in vacuum to a gum
2. 2
   workup.ADDITIONdiluted with ethyl acetate (50 mL) and 10% potassium carbonate solution (10 mL)
3. 3
   기타The ethyl acetate layer was then separated
4. 4
   건조dried over sodium sulphate
5. 5
   농축concentrated in vacuum
6. 6
   기타to give a colourless gum
7. 7
   기타The gum was chromatographed on a 25 g silica column in a gradient of 2-15% methanol in dichloromethane
8. 8
   기타was collected

실험 절차

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-8-azabicyclo[3.2.1]octan-3-amine (200 mg, 0.5 mmol) in formalin solution (5 mL) and formic acid (5 mL) was heated to 80° C. for 1 h. The reaction was then concentrated in vacuum to a gum, diluted with ethyl acetate (50 mL) and 10% potassium carbonate solution (10 mL) and shaken. The ethyl acetate layer was then separated, dried over sodium sulphate and concentrated in vacuum to give a colourless gum. The gum was chromatographed on a 25 g silica column in a gradient of 2-15% methanol in dichloromethane. The slower running peak was collected to give 8-(5-bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-N-methyl-8-azabicyclo[3.2.1]octan-3-amine (165 mg, 0.405 mmol, 81%). 1H NMR (CDCl3) δ: 1.35 (2H, t, J=12 Hz), 1.5-1.7 (4H, m), 1.8-2.0 (6H, m), 2.1 (3H, s), 2.5 (2H, br m), 3.1 (2H, br m), 4.7 (2H, br m), 7.3 (1H, s), 8.4 (1H, s).

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