반응 #1015783

반응 방정식

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

(2-methoxy-3-pyridyl)boronic acid

triphenylphosphine

→

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

수율 36.5%

용매

ethyl acetate

sodium bicarbonate

DMSO water

dimethoxyethane

sodium carbonate

반응 조건

후처리

1. 1
   workup.STIRRINGshaken
2. 2
   기타The ethyl acetate layer was then separated
3. 3
   건조dried over sodium sulphate
4. 4
   농축concentrated in vacuum
5. 5
   기타to give a gum
6. 6
   기타purified by reverse phase HPLC
7. 7
   기타The main peak was collected
8. 8
   농축concentrated in vacuum

실험 절차

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-N-methyl-8-azabicyclo[3.2.1]octan-3-amine (82.5 mg, 0.20 mmol) in dimethoxyethane (4 mL) and 2 M sodium carbonate solution (1 mL) was treated with (2-methoxy-3-pyridyl)boronic acid (134 mg, 0.75 mmol) and palladium (II) acetate (12 mg, 0.053 mmol), triphenylphosphine (12 mg) and the reaction was stirred in a microwave at 85° C. over 1 h. The reaction was then diluted with ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL) and shaken. The ethyl acetate layer was then separated, dried over sodium sulphate and concentrated in vacuum to give a gum. The gum was dissolved in DMSO/water 1:1 (2.5 mL) and purified by reverse phase HPLC. The main peak was collected and concentrated in vacuum to give N-cyclobutyl-8-[5-(2-methoxy-3-pyridyl)thieno[2,3-d]pyrimidin-4-yl]-N-methyl-8-azabicyclo[3.2.1]octan-3-amine as a gum (32 mg, 0.073 mmol, 36%). LCMS RT=4.76 min. M+1=436. 1H NMR (CDCl3) δ: 1.1 (2H, t, J=12 Hz), 1.3-1.9 (1H, m), 1.9 (3H, s), 2.2 (1H, br m), 2.9 (1H, br m), 3.9 (3H, s), 4.3 (2H, br s), 7.0 (1H, q, J=6 Hz, J′=4 Hz), 7.25 (1H, s), 7.55 (1H, d, J=6 Hz), 8.2 (1H, d, J=4 Hz), 8.5 (1H, s).

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