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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Isonipecotic acid is a specific GABAA receptor agonist.
Synonyms: 4-Piperidinecarboxylic acid; 4-Carboxypiperidine; Hexahydroisonicotinic acid
4.5
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 498-94-2 |
Formula : | C6H11NO2 |
M.W : | 129.16 |
SMILES Code : | O=C(C1CCNCC1)O |
Synonyms : |
4-Piperidinecarboxylic acid; 4-Carboxypiperidine; Hexahydroisonicotinic acid
|
MDL No. : | MFCD00006004 |
InChI Key : | SRJOCJYGOFTFLH-UHFFFAOYSA-N |
Pubchem ID : | 3773 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
92% | With sodium hydroxide In water at 0 - 30℃; for 3 h; | Example 1 — Preparation of 1-(Ethoxycarbonyl) piperidine-4-Carboxylic AcidTo a solution of (154.8 gm) Sodium hydroxide in (750 ml) purified water, Isonipecotic acid(250gm) was added at 0-10°C, followed by the slow addition of ethyl chloroformate (231 ml) at 5-20°C. The reaction mixture was heated to 20-30°C and maintained for 3 hrs at the sametemperature. After completion of the reaction, the reaction mass was acidified to a pH 1-2 byaddition of hydrochloric acid. Then toluene (750 ml) was added to the reaction mass and stirred for15 minutes at 25-30 °C. The organic layer was separated and concentrated under vacuum at below70°C to obtain a residue. The resi4ue_was_mixed. with cyclohexane (1250 ml) at 60-70°C, thencooled to 25-30°C and maintain for I hour at the same temperature. The resulted contents werefiltered, and washed with cyclohexane (1250 ml) and dried at 50-55°C. Percentage Yield: 92percent |
91.9% | With sodium carbonate In tetrahydrofuran; water at 20℃; for 2 h; | 5.16 g (40 mmol) of the starting material 4-piperidinecarboxylic acid was added to a 100 ml round bottom flask, Na2CO3 5.04 g (48 mmol) and 40 mL of water was added. 5.13 g (48 mmol) was dissolved in 40 mL of tetrahydrofuran, added dropwise to a round bottom flask and stirred at room temperature for 2 h. The reaction was evaporated to remove tetrahydrofuran rotary end, was added 60mL of water, adjusted to pH 2 with 2MHCl, extracted with EA (30mL × 3), combined EA phases were dried over anhydrous MgSO4, filtered and rotary-dry products acquired Intermediate 1 as a white solid. Yield 91.9percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.1% | With hydrogen;palladium 10% on activated carbon; In water; at 16 - 25℃; | Load isonipicotic acid (1 kg, 7.74 mol), water (10 L), formaldehyde (37percent solution in water, 720 g, 8.87 mol, 1.15 eq. ) and wet Pd/C catalyst (10percent; 55percent paste, 100 g) into a stainless steel hydrogenation reactor. Pressurize the reactor with H2 (3 bar) and stir the reaction mixture overnight at 200-300 rpm at 16-25°C. Stop the reaction and filter off the catalyst. Wash the filtrate with water (500 ml) and concentrate under vacuum. Distill off the remaining water from the residue using ethanol (2x 1 L). Dry the solid overnight under vacuum at 50°C to obtain the title product as an off-white solid (1087 g, 98. 1percent yield). |
76% | With hydrogen;palladium 10% on activated carbon; In water; at 20℃; under 3102.97 Torr; for 18h; | Isonipecotic acid (50 g, 0.387 mole) was dissolved in water (500 ml) and 37percent formaldehyde (125 ml). 10percent Palladium on carbon (50 g) was added and the mixture was shaken under a hydrogen atmosphere at 60 psi at room temperature for 18 hours. [00375] The catalyst was filtered, washed with water, and the filtrate was concentrated under reduced pressure. The residue was slurried in water and concentrated in vacuo. The residue was slurried in ethanol and concentrated in vacuo to give a white solid. Drying under vacuum at ambient temperature for 18 h gave 42.2 g (76percent) of a white solid, [00376] mp 173-5° C. MS(m/e): 143 (M+). [00377] Analysis for C7H13NO2: [00378] Calcd: C, 58.72; H, 9.15; N, 9.78; Found: C, 58.24; H, 9.59; N. 9.71. |
18% | In formic acid; water; for 20h;Heating / reflux; | Reference Example 249: l-MethvI-piperidine-4-carboxylic acid . A solution of 4-piperidine carboxylic acid (1.0 g, 7.75 mmol) in a mixture of90percent formic acid (3 mL) and 37percent formaldehyde solution (2 mL) was heated at reflux for 20 h. The volatiles were removed in vacuo and cone. HCl added to the residue. The reaction mixture was extracted with dichloromethane and washed with brine solution. The organic layer was dried over sodium sulfate, filtered and dried to afford 1-methyl- piperidine-4-carboxylic acid (0.20 g, 18 percent). |
With hydrogen;10% palladium on activated charcoal; In water; at 20℃; under 2250.23 Torr; | Compounds 108, 109, 143, 144 and 145 were synthesized by using the materials that have a substituent corresponding to these compounds, according to the following production scheme. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; | D. To a solution of 1 g of isonipecotic acid in 10 ml of water was added 1.07 g potassium carbonate and this was stirred for 15 minutes at room temperature. 0.961 g <strong>[1184-90-3]aminoiminomethanesulfonic acid</strong> was then added portionwise over 20 minutes. The solution was stirred for 2 hours at room temperature, concentrated in vacuo to one-half of the original volume and the resulting precipitate collected by filtration. The resulting solid wasrecrystallized from water to give N-amidino-4-piperidine carboxylic acid. | |
With potassium carbonate; In water; | A. N-amidino-4-piperidine carboxylic acid was prepared essentially by the method of Miller, et al, Synthesis, 777 (1986), which is incorporated herein by reference. To a solution of 1 g of isonipecotic acid in 10 ml of water was added 1.07 g potassium carbonate and this was stirred for 15 minutes at room temperature. 0.961 g <strong>[1184-90-3]aminoiminomethanesulfonic acid</strong> was then added portionwise over 20 minutes. The solution was stirred for 2 hours at room temperature, concentrated in vacuo to one-half of the original volume and the resulting precipitate collected by filtration. The resulting solid was recrystallized from water to give N-amidino-4-piperidine carboxylic acid. This was dissolved in an aqueous solution of tetrahydrofuran. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of <strong>[19064-24-5]2,6-difluoronitrobenzene</strong> (272 mg, 1.71 mmol) in DMSO (2 mL) was added methyl-3-amino-3-phenylpropanoate (553 mg, 2.57 mmol) and potassium carbonate (709 mg, 5.13 mmol), and the suspension stirred at room temperature for 24 hours. 4-Piperidinecarboxylic acid (335 mg, 2.59 mmol) was added, and the resulting suspension stirred at room temperature for 24 hours, and then heated at 100 C. for 3 hours. The suspension was cooled to room temperature, and diluted with water. The aqueous solution was extracted with ethyl acetate, and the separated aqueous layer acidified with dilute hydrochloric acid (pH<4), and re-extracted with ethyl acetate. The second organic extracts were evaporated in vacuo, and the residue purified by flash column chromatography on silica gel, eluding with a mixture of dichloromethane and methanol (96:4) to afford the title compound, 1H NMR: (CDCl3) 7.36-7.22 (m, 5H), 7.02 (t, J=8.06, 1H), 6.34 (dd, J=8.06, 1.10, 1H), 6.19 (d, J=8.06, 1H), 4.89-4.85 (m, 1H), 3.66 (s, 3H), 3.25-3.21 (m, 2H), 2.87-2.77 (m, 4H), 2.48-2.41 (m, 1H), 2.02-1.82 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To isonipecotic acid (41.5 g; 320 mmol) was added 1,4-dioxane (200 mL). Thus, an inhomogeneous solution was obtained. Thereto was added 41.5 mL of concentrated sulfuric acid over 30 minutes. Into this inhomogeneous solution was bubbled 100 g of isobutene over 5 hours. After completion of the bubbling, the mixture was cooled to 0° C. and 750 mL of 2-N aqueous NaOH solution was added thereto. The resultant mixture was ascertained to be basic. Thereafter, a reaction product was extracted with 500 mL of diethyl ether, and the extract was dried with sodium sulfate and then concentrated to obtain 5.98 g of t-butyl isonipecotate as the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[00226] To a suspension of isonipecotic acid (300 mg, 2.3mmol, 1 eq) in DMA (15mL) was added pyrazine 2-carboxaldehyde (377 mg, 3.5mmol, 1.5eq) and acetic acid (133uL, 2.3 mmol, 1 eq). After 5 min, sodium triacetoxyborohydride (738 mg, 3.5mmol, 1.5 eq) was added and the reaction mixture stirred overnight. The reaction mixture was concentrated under reduced pressure and the residue dissolved in MeOH (3ml_) and loaded onto SCX-2 cartridge. The cartridge was washed with MeOH, and the compound eluted using 1 M ammonia in methanol. The product-containing fractions were concentrated under reduced pressure to give the 1-pyrazin-2-ylmethyl-piperidine-4-carboxylic acid (435 mg) as a brown gum. AnalpH2_MeOH_4MIN Rt: 0.33 min, m/z 222.3 [M+H]+ The crude product was used directly in subsequent reactions without further purification. |
Tags: Isonipecotic acid | 4-Piperidinecarboxylic acid | GABA Receptor | Membrane Transporter/Ion Channel | Neuronal Signaling | Tumor Development and Microenvironment Evolution | 498-94-2
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