* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 20℃;
2-(Butyloxy)-8-(methyloxy)-1 H-purin-6-amine (300mg, 1.264 mmol), (1-ethyl-4- piperidinyl)methanol (362 mg, 2.53 mmol) and tributylphosphine (0.624 ml, 2.53 mmol) were dissolved in THF (12ml). 1 ,1 '-(Azodicarbonyl)dipiperidine (638 mg, 2.53 mmol) was added and the reaction mixture stirred at rt overnight. The solvent was removed in vacuo and the residue purified by column chromatography, loading in dichloromethane and purified on Flashmaster Il silica (Si) 2Og using a 0-100% ethyl acetate in cyclohexane+0-20% methanol (+1 %Et3N) gradient over 30 mins. The appropriate fractions were combined and evaporated in vacuo. The material (300mg) was dissolved in 1 :1 MeOH:DMSO 3ml and re-purified by Mass Directed AutoPrep (Method A). The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus to give the title compound as a clear gum (60mg). LCMS (System A): tRET = 0.57 min; MH+ 363
2-[(1 S)-1-Methylbutyl]oxy}-8-(methyloxy)-1 H-purin-6-amine trifluoroacetate (250mg, 0.684 mmol) was dissolved in methanokdichloromethane (1 :1 , 3ml) and loaded onto an aminopropyl SPE (2g) which had been pre-conditioned with methanol. The cartridge was eluted with methanokdichloromethane (1 :1 ) and the solvent concentrated to give as a cream solid (173mg). The solid (173mg, 0.684mmol), 1- ethyl-4-piperidinyl)methanol (196 mg, 1.369 mmol) and tributylphosphine (0.338 ml, 1.369 mmol) were dissolved in THF (6ml) and stirred at rt for 30 mins. 1 ,1'- (Azodicarbonyl)dipiperidine (345 mg, 1.369 mmol) was added and the reaction mixture stirred at rt overnight. The solvent was removed in vacuo and the residue purified by column chromatographyon silica, loading in dichloromethane and eluting with a gradient of 0-100% ethyl acetate in cyclohexane+0-20% methanol(+1 %Et3N) over 30 mins on the Flashmaster II. The appropriate fractions were combined and evaporated in vacuo. The material was dissolved in 1 :1 MeOH:DMSO (2ml) and re- purified by Mass Directed AutoPrep (Method A). The solvent was concentrated in vacuo to give the title compound as a brown gum (32mg). LCMS (System A): tRET = 0.63min; MH+ 377
[00500] (l-Ethyl-piperidin-4-yl)-methanol (39): To a magnetically stirred solution of methyl isonipecotate 38 (4 g, 23.4 mmol) in anhydrous THF (350 mL) was added LAH (1 g) in portions at O0C. Upon completion, 20 mL water was added, followed by 20 mL NaOH (15%) and 20 mL water. The solid was filtered off and solvent rotovaped. The residue (l-ethylpiperidin-4-yl)methanol 39 was purified by silica gel flash chromatography (0-100% MeOH/DCM).
[00501] 4-(l-Ethyl-piperidin-4-ylmethoxy)-2-methyl-phenylamine (41): To a magnetically stirred solution of (l-ethylpiperidin-4-yl)methanol 39 (0.305 g, 2.13 mmol) in DMF (4 mL) was added NaH (85 mg, 2.13 mmol). The mixture was stirred 30 minutes at room temperature before adding 4-fluoro-2-methyl-l -nitrobenzene (0.3 g, 1.94 mmol). Upon completion, the reaction was quenched with water and extracted with DCM several times. The organic phases were combined and the solvent concentrated in vacuo. The residue l-ethyl-4-[(3-methyl-4-nitrophenoxy)methyl]piperidine 40 was purified by silica gel flash chromatography (0- 100% MeOH/DCM). It was converted to 41, using conditions as described for compound 36b (Scheme 10).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
