* 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.
Multi-step reaction with 4 steps
1: dichloromethane; tetrahydrofuran / 10 h / 20 °C
2: acetone / 15 h / 20 °C
3: sodium tetrahydroborate / methanol / 3 h / 0 °C
4: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C
Multi-step reaction with 3 steps
1: acetone / 15 h / 20 °C
2: sodium tetrahydroborate / methanol / 3 h / 0 °C
3: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C
With trifluoroacetic acid In dichloromethane at 20℃; for 0.5h;
12 Preparation of (1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanamine
To a mixture of tert-butyl ((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl) methyl)carbamate (200 mg, 0.66 mmol) in DCM (10 mL) was added TFA (5 mL), then the reaction mixture was stirred at RT for 0.5 h. The reaction mixture was concentrated in vacuo to give (1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanamine as a purple solid (crude 250 mg, quantitative yield). LC-MS (ESI): m/z (M+1)+ = 204.50
N-ethyl-5,6-difluoro-N-(4-(trifluoromethyl)benzyl)pyrimidin-4-amine[ No CAS ]
[ 153196-51-1 ]
N<SUP>4</SUP>-((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methyl)-N<SUP>6</SUP>-ethyl-5-fluoro-N<SUP>6</SUP>-(4- (trifluoromethyl)benzyl)pyrimidine-4,6-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50%
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 90℃;
D5-1-1 N4-((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methyl)-N6-ethyl-5-fluoro-N6-(4- (trifluoromethyl)benzyl)pyrimidine-4,6-diamine, 2D2-1.
N-ethyl-5,6-difluoro-N-(4-(trifluoromethyl)benzyl)pyrimidin-4-amine (A3-2) (1.3 g, 4.0 mmol) and (1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanamine (2D1) (1.1 g, 4.0 mmol), were added to a solution of DIEA (2.6 g, 20.0 mmol) in DMSO (20 mL) and the reaction was stirred at 90 °C on. H2O (60 mL) was added and the mixture was extracted with EA (3 x 20 mL). The combined organic layer was washed with brine (3 x 20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The remaining residue was purified by Flash CC (MeOH:DCM=1:30) to yield 2D2-1 (1.0 g, 50%) as a yellow oil.LCMS: MS Calcd.: 499; MS Found: 500([M+H]+).
(3RS,4RS)-1-benzyl-4-(((6-(ethyl(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)piperidine-3,4-diol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 2 steps
1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 90 °C / Microwave irradiation
2: potassium carbonate; potassium hexacyanoferrate(III); 4-[(R)-[(2R,4R,5S)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]-1-[(R)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]phthalazine; potassium osmate; methanesulfonamide / <i>tert</i>-butyl alcohol; water / 0 - 20 °C
2-((3R,4R)-4-(((6-(ethyl(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide[ No CAS ]
2-((3S,4S)-4-(((6-(ethyl(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 5 steps
1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 90 °C / Microwave irradiation
2: potassium carbonate; potassium hexacyanoferrate(III); 4-[(R)-[(2R,4R,5S)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]-1-[(R)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]phthalazine; potassium osmate; methanesulfonamide / <i>tert</i>-butyl alcohol; water / 0 - 20 °C
3: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 760.05 Torr
4: potassium carbonate / N,N-dimethyl-formamide / 2 h / 25 °C
5: CHIRALPAK IG / hexane; ethanol; diethylamine / Resolution of racemate
2-((3RS,4RS)-4-(((6-(ethyl(((1r,4R)-4-(trifluoromethyl)cyclohexyl)methyl)amino)-5-fluoropyrimidin-4-yl)amino)methyl)-3,4-dihydroxypiperidin-1-yl)acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Multi-step reaction with 4 steps
1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 90 °C / Microwave irradiation
2: potassium carbonate; potassium hexacyanoferrate(III); 4-[(R)-[(2R,4R,5S)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]-1-[(R)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxy-4-quinolinyl)methoxy]phthalazine; potassium osmate; methanesulfonamide / <i>tert</i>-butyl alcohol; water / 0 - 20 °C
3: palladium 10% on activated carbon; hydrogen / methanol / 20 °C / 760.05 Torr
4: potassium carbonate / N,N-dimethyl-formamide / 2 h / 25 °C
N-ethyl-5,6-difluoro-N-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)pyrimidin-4-amine[ No CAS ]
[ 153196-51-1 ]
N<SUP>4</SUP>-((1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methyl)-N<SUP>6</SUP>-ethyl-5-fluoro-N<SUP>6</SUP>-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)pyrimidine-4,6-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 90℃; Microwave irradiation;
N4-((1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)methyl)-N6-ethyl-5-fluoro-N6- (((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)pyrimidine-4,6-diamine) AD-3
A solution of (1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanamine--N-ethyl- 5,6-difluoro-N-(((1r,4r)-4-(trifluoromethyl)cyclohexyl)methyl)pyrimidin-4-amine AD-1 (800 mg, 2.91 mmol), N-ethyl-5,6-difluoro-N-(((1r,4r)-4- (trifluoromethyl)cyclohexyl)methyl)pyrimidin-4-amine AD-2 (940 mg, 2.91 mmol) and DIEA (1.9 g, 14.6 mmol) in DMSO (20 mL) heated to 90 ° in a microwave reactor on. Thereafter, H2O (50 mL) was added and the mixture was extracted with EA (3 x 20 mL). The combined organic layer was washed with brine (3 x 20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by Flash CC (EA:PE=1:2 to MeOH:DCM=1:30) to afford AD-3. LCMS: MS Calcd.: 505; MS Found: 506 ([M+H]+).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
