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CAS No. : | 111669-25-1 | MDL No. : | MFCD03407996 |
Formula : | C14H22N4O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CBTYZJKYXVDWOG-UHFFFAOYSA-N |
M.W : | 278.35 | Pubchem ID : | 2756375 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium cyanoborohydride; In methanol; at 20℃; for 48h; | Example 34.1 : 4-(3-Ethylamino-pyridin-2-yl)-piperazine-l-carboxylic acid tert-butyl ester. To a mixture of 4-(3-amrno-pyridm-2-yl)-piperazme-l-carboxylic acid tert-butyl ester (2,0 g, 7.18 mmol), acetaldehyde (0.81 mL, 0.014 mol) and methanol (30 mL) was added sodium cyanoborohydride (1.36 g, 0.022 mol). The reaction mixture was stirred at room temperature for 2 days and then diluted with ethyl acetate, washed with water and washed with brine. The organic layer was separated, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel using hexanes: ethyl acetate (80:20) to give 4-(3-ethylamino-pyridm-2-yl)-piperazme-l-carboxylic acid tert-butyl ester (2.0 g, 91 %). GC/MS mfz 306, 223, 162, 150, 137, 120, 57. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; for 2h; | A mixture of tert-butyl 4-(3-nitropyridin-2-yl)piperazine-l -carboxylate 5 (350 mg, 1.14 mmol), Pd/C (60.4 mg, 10%, 0.0568 mmol) and MeOH (6 ml) was subjected to the hydrogenation condition with hydrogen balloon at room temperature. After stirring for 2 h, the resulting solution was filtered through celite. The resulting organic solution was concentrated under reduced pressure and purified by silica gel column chromatography (Hexane/EtOAc/CH2Cl2 = 1 : 1 : 1) to give tert-butyl 4-(3-aminopyridin-2-yl)piperazine-l -carboxylate (246 mg, 78%) as a white powder. MS (EI) for Ci4H22 402: 279.2 (MH+). |
69% | With hydrogen;palladium on activated charcoal; In ethanol; under 1034.32 Torr; for 2h; | Example 18.1: 4-(3-Ammo-pyridin-2-yl)-piperazine-l-carboxylic acid tert-butyl ester. A mixture of 4-(3-nitro-pyridin-2-yl)-piperazine-l-carboxylic acid tert-tmtyl ester (4.0 g, 12,97 mmol), palladium (on activated carbon, 500 mg) and ethanol (150 mL) was shaken under 20 psi of hydrogen for 2 hours. The reaction mixture was filtered through Diatomaceous earth and concentrated to give 4-(3-amino-pyridin-2-yl)-piperazine-l- carboxylic acid tert-butyl ester (2.5 g, 69 %). GC/MS m/z 278, 205, 134, 148, 109, 93, 57. |
With palladium(II) hydroxide; In methanol; cyclohexene; at 70℃; for 2h; | Synthesis of 3-Amino-2-(Boc-piperazinyl)pyridine 7: 3-Nitro-2-(Boc-piperazine)pyridine 6 (1.765 g, 5.72 mmol) was dissolved in methanol (15 mL) at room temperature. Then Pd(OH)2 (1.234 g) and cyclohexene (2.0 mL, 19.52 mmol) were added. The resulting mixture was heated at 70 C. for 2 h. The mixture was concentrated to remove the solvent. DCM was added and then it was filtered through a pad of silica gel, washed with DCM and 10% MeOH/DCM. The collected solution was concentrated and dried under high vacuum to afford a slight pink solid as the product (1.384 g, 87% yield). 1H-NMR (CDCl3): 7.794 (dd, J=5.0 Hz and 1.5 Hz, 1 H, Ar-H), 6.956 (dd, J=7.5 Hz and 1.5 Hz, 1 H, Ar-H), 6.854 (dd, J=7.5 Hz and 5.0 Hz, 1 H, Ar-H), 3.783 (br, 2 H, NH2), 3.571 (t, J=4.5-5.0 Hz, 4 H, 2 CH2), 3.059 (t, J=4.5-5.0 Hz, 4 H, 2 CH2), 1.482 (s, 9 H, 3 CH3). LC-MS: 279.2 (MH+). (ref. Romero D. L. et al. J. Med. Chem. 37, 999-1014, 1994.) Synthesis of 2-(Boc-piperazinyl)-3-(isopropylamino)pyridine 4: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | 3-amino-2-(Boc-piperazine)pyridine 7 (3.813 g, about 11.16 mmol, crude) was dissolved in dichloroethane (75 mL). Acetone (1.7 mL, 23.12 mmol) was added, followed by an addition of HOAc (1.0 mL, 17.45 mmol) at room temperature. After about 10 min, NaBH(OAc)3 (7.46 g, 33.44 mmol) was added. An additional amount of dichloroethane (25 mL) was added. The resulting mixture was stirred at room temperature for 64 h. 5% aqueous NaHCO3 was added to quench the reaction. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2*50 mL). The combined organic solution was washed with brine, dried over anhydrous Na2SO4, concentrated. The residue was purified via flash column chromatography over silica gel with 5-35% ethyl acetate in hexane to afford the product as solid in quantitative yield. 1H-NMR (CDCl3): 7.673 (dd, J=5.0 Hz and 1.5 Hz, 1 H, Ar-H), 6.904 (dd, J=8.0 Hz and 5.0 Hz, 1 H, Ar-H), 6.812 (dd, J=8.0 Hz and 1.5 Hz, 1 H, Ar-H), 4.150 (d, J=7.5 Hz, 1 H, NH), 3.569-3.517 (m, 5 H, 2CH2 and CH), 2.997 (t, J=5.0 Hz, 4 H, 2 CH2), 1.477 (s, 9 H, 3 CH3), 1.23 (d, J=6.0 Hz, 6 H, 2 CH3). (ref. Romero D. L. et al. J. Med. Chem. 37, 999-1014, 1994.) Synthesis of 2-piperazinyl-3-(isopropylamino)pyridine 8: |
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