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CAS No. : | 82205-58-1 | MDL No. : | MFCD00053059 |
Formula : | C9H12N4O2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | YEPRCPIKTUGVHG-UHFFFAOYSA-N |
M.W : | 208.22 | Pubchem ID : | 2928799 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
100% | 309. Step 2: /V-(5-nitropyridin-2-yl)piperazine (B-3)To compound B-2 (19.45 g, 0.0631 mol) dissolved in CH2CI2 (250 ml_) and cooled to 0 0C was added trifluoroacetic acid (50 ml_). The resulting reaction mixture was stirred at RT for 16 h then concentrated. The crude product was dissolved in CH2CI2 (250 ml_) and made basic with the addition of 1 N aqueous NaOH (200 ml_) and 3 N aqueous NaOH (100 ml_). The layers were separated, and the aqueous solution extracted with CH2CI2. The combined organic extract was dried (MgSO4), filtered, and concentrated to give the product N-(2-fluorophenyl)-4-(5-nitropyridin-2-yl)piperazine-1-carboxamide (B- 3) as a yellow solid (13.13 g, 100% yield). MS (M+1): 209 | |
100% | Step 2: N-(5-nitropyridin-2-yl)piperazine (B-3)To compound B-2 (19.45 g, 0.0631 mol) dissolved in CH2C12 (250 mL) and cooled to 0 C was added trifiuoroacetic acid (50 mL). The resulting reaction mixture was stirred at RT for 16 h then concentrated. The crude product was dissolved in CH2C12 (250 mL) and made basic with the addition of 1 N aqueous NaOH (200 mL) and 3 N aqueous NaOH (100 mL). The layers were separated, and the aqueous solution extracted with CH2CI2. The combined organic extract was dried (MgS04), filtered, and concentrated to give the product N-(2-fluorophenyl)- 4-(5-mtropyridin-2-yl)piperazine-l-carboxamide (B-3) as a yellow solid (13.13 g, 100% yield). MS (M+l): 209. | |
84% | In a 250 mL round-bottom flask, a dichloromethane: TFA (10:1) (50 mL) solution of compound 3a (1100 mg, 3.57 mmol) was stirred under argon at rt for 2 h. The solvent was concentrated and re-evaporated with dichloromethane (2x 20 mL), then the reaction mixture was extracted with dichloromethane (50 mL) and washed with Na2CO3 (30 mL). The organic layer was dried over MgSO4, filtered and evaporated in vacuum to afford a yellow solid: 625 mg (84%) yield. 1H NMR CDCl3 delta = 9.02 (1H, d, J = 2.9 Hz), 8.17 (1H, dd, J1, J2 = 2.9 Hz), 6.54 (1H, d, J = 9.5 Hz), 3.73 (4H, t, J = 10.2 Hz), 2.97 (4H, t, J = 10.2 Hz) (as in many cases herein, NH exchanges and is not always obeserved). 13C NMR CDCl3 delta = 164.2, 146.5, 135.0, 133.0, 104.5, 46.0 (2C), 45.8 (2C). HRMS m/z calculated for C9H13N4O2 (MH+): 209.1033, Found: 209.1032. |
71% | With trifluoroacetic acid; In dichloromethane; at 0 - 20℃; for 4h; | Compound from Description 43 (0.78g) was dissolved in dry DCM (18ml), cooled in an ice bath to ~ O0C before adding TFA (2ml) slowly over 5 minutes. The resultant solution was then allowed to warm up to R.T. and was stirred for 4 hours, under argon. The reaction solution was poured slowly onto ice saturated potassium carbonate before extracting with DCM (3x 50ml). The combined extracts were dried over anhydrous magnesium sulphate, filtered and solvent removed in vacuo to afford the title compound as a yellow solid in 71%.1H NMR ( 400MHz, CDCI3) delta 9.03 ( d, 1H), 8.20 (dd, 1 H), 6.55 (d, 1 H), 3.75 ( m, 4H), 2.98 (m, 4H) |
71% | With trifluoroacetic acid; In dichloromethane; at 0 - 20℃; for 4.08333h; | Compound from Description 43 (0.78g) was dissolved in dry DCM (18ml), cooled in an ice bath to ~ 00C before adding TFA (2ml) slowly over 5 minutes. The resultant solution was then allowed to warm up to RT. and was stirred for 4 hours, under argon. The reaction solution was poured slowly onto ice saturated potassium carbonate before extracting with DCM (3x 50ml). The combined extracts were dried over anhydrous magnesium sulphate, filtered and solvent removed in vacuo to afford the title compound as a yellow solid in 71%.1 H NMR ( 400MHz, CDCI3) delta 9.03 ( d, 1 H), 8.20 (dd, 1 H), 6.55 (d, 1 H), 3.75 ( m, 4H), 2.98 (m, 4H) |
With trifluoroacetic acid; In dichloromethane; at 0℃; for 1.08333h; | Step 2: 4-(5-Nitropyridin-2-yl)piperazine: To a stirred solution of Step 1 intermediate (32 g, 103.896 mmol) in dichloromethane (200 ml) was added trifiuoroacetic acid (96 ml) at 0 C over 5 min. The reaction mixture was stirred for another 1 h at the same temperature. The residue obtained after evaporation of the solvent was dissolved in ethyl acetate (180 ml) and washed with saturated NaHCO3 (2 x 100 ml) and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure to afford 19.5 g of the desired salt as a yellow solid. | |
Step B: N-(5 -nitropyridin-2-yl)piperazineTo t-butyl 4-(5-nitropyridin-2-yl)piperazine-l -carboxylate (19.45 g, 0.0631 mol) dissolved in CH2CI2 (250 mL) and cooled to 0 C was added trifluoroacetic acid (50 mL). The resulting reaction mixture was stirred at RT for 16 h then concentrated. The crude product was dissolved in CH2CI2 (250 mL) and made basic with the addition of 1 N aqueous NaOH (200 mL) and 3 N aqueous NaOH (100 mL). The layers were separated, and the aqueous solution extracted with CH2CI2. The combined organic extract was dried (MgS04), filtered, and concentrated to yield N-(2-fluorophenyl)-4-(5-nitropyridin-2-yl)piperazine-l-carboxamide as a yellow solid. LC/MS - 209 [M+l]. |