*Storage: Keep in dark place,Sealed in dry,Room Temperature.
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Picolinic acid is a tryptophan-derived metabolite with anti-infective and immunomodulatory properties. It alters the structure and function of zinc-finger proteins by binding zinc.
Synonyms: PCL 016
4.5
*For Research Use Only !
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Surveying the scope of aromatic decarboxylations catalyzed by prenylated-flavin dependent enzymes
Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto , et al. Faraday Discuss.,2024,252,208-222.
Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.
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Purchased from AmBeed: 27916-43-4 ; 2438-05-3 ; 501-89-3 ; 42287-94-5 ; 776-79-4 ; 53473-36-2 ; 7251-61-8 ; 42287-97-8 ; 1621-91-6 ; 37718-11-9 ; 288-13-1 ; 86-73-7 ; 104-53-0 ; 2018-90-8 ; 87-66-1 ; 135-19-3 ; 1664-57-9 ; 289-80-5 ; 693-95-8 ; 55-22-1 ; 102-93-2 ; 1477-50-5 ; 1632-76-4 ; 4780-79-4 ; 16642-79-8 ; 3581-89-3 ; 501-97-3 ; 771-50-6 ; 98-98-6 ; 619-64-7 ; 100-51-6 ; 402-45-9 ; 59-67-6 ; 93-60-7 ; 273-53-0 ; 2084-13-1 ; 51-17-2 ; 2459-09-8 ; 2459-07-6 ; 95-16-9 ; 459-31-4 ; 90-05-1 ; 150-76-5 ; 103-25-3 ; 271-44-3 ; 6293-56-7 ; 2550-26-7 ; 288-32-4 ; 501-52-0 ; 2001-32-3 ; 1592-38-7 ; 95-15-8 ; 91-19-0 ; 1122-61-8 ; 3724-19-4 ; 20173-24-4 ; 118-31-0 ; 6125-24-2 ; 60-12-8 ; 90-15-3 ; 120-72-9 ; 822-36-6 ; 288-47-1 ; 288-42-6 ; 2038-57-5 ; 38628-51-2 ; 1929-29-9 ; 15009-91-3 ; 1505-50-6 ; 581-40-8 ; 616-47-7 ; 1571-33-1
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Tian, Gui-Long ; Hsieh, Chia-Ju ; Taylor, Michelle , et al. Eur. J. Med. Chem.,2023,261,115751.
Abstract: The difference in the secondary binding site (SBS) between the dopamine 2 receptor (D2R) and dopamine 3 receptor (D3R) has been used in the design of compounds displaying selectivity for the D3R versus D2R. In the current study, a series of bitopic ligands based on Fallypride were prepared with various secondary binding fragments (SBFs) as a means of improving the selectivity of this benzamide analog for D3R versus D2R. We observed that compounds having a small alkyl group with a heteroatom led to an improvement in D3R versus D2R selectivity. Increasing the steric bulk in the SBF increase the distance between the pyrrolidine N and Asp110, thereby reducing D3R affinity. The best-in-series compound was (2S,4R)-trans-27 which had a modest selectivity for D3R versus D2R and a high potency in the β-arrestin competition assay which provides a measure of the ability of the compound to compete with endogenous dopamine for binding to the D3R. The results of this study identified factors one should consider when designing bitopic ligands based on Fallypride displaying an improved affinity for D3R versus D2R.
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Keywords: Dopamine 2 receptor ; Dopamine 3 receptor ; Fallypride ; Bitopic ligands ; PET imaging
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Purchased from AmBeed: 89031-84-5 ; 40216-83-9 ; 88-13-1 ; 135042-17-0 ; 110-52-1 ; 488-93-7 ; 18742-02-4 ; 98-98-6 ; 86864-60-0 ; 62-23-7 ; 29886-64-4 ; 59741-04-7 ; 4385-62-0 ; 15268-31-2 ; 134441-72-8 ; 54751-01-8 ; 166173-78-0 ; 213131-32-9 ; 98-98-6 ; 69966-55-8 ; 154342-67-3
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Structure activity relationship of pyrazinoic acid analogs as potential antimycobacterial agents
Hegde, Pooja V. ; Aragaw, Wassihun W. ; Cole, Malcolm S. , et al. Bioorgan. Med. Chem.,2022,74,117046.
Abstract: Tuberculosis (TB) remains a leading cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a critical component of the first-line TB treatment regimen because of its sterilizing activity against non-replicating Mycobacterium tuberculosis (Mtb), but its mechanism of action has remained enigmatic. PZA is a prodrug converted by pyrazinamidase encoded by pncA within Mtb to the active moiety, pyrazinoic acid (POA) and PZA resistance is caused by loss-of-function mutations to pyrazinamidase. We have recently shown that POA induces targeted protein degradation of the enzyme PanD, a crucial component of the CoA biosynthetic pathway essential in Mtb. Based on the newly identified mechanism of action of POA, along with the crystal structure of PanD bound to POA, we designed several POA analogs using structure for interpretation to improve potency and overcome PZA resistance. We prepared and tested ring and carboxylic acid bioisosteres as well as 3, 5, 6 substitutions on the ring to study the structure activity relationships of the POA scaffold. All the analogs were evaluated for their whole cell antimycobacterial activity, and a few representative mols. were evaluated for their binding affinity, towards PanD, through isothermal titration calorimetry. We report that analogs with ring and carboxylic acid bioisosteres did not significantly enhance the antimicrobial activity, whereas the alkylamino-group substitutions at the 3 and 5 position of POA were found to be up to 5 to 10-fold more potent than POA. Further development and mechanistic anal. of these analogs may lead to a next generation POA analog for treating TB.
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Keywords: Tuberculosis ; Pyrazinoic acid ; pyrazinamide
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Purchased from AmBeed: 16289-54-6 ; 5521-55-1 ; 22047-25-2 ; 98-80-6 ; 40155-47-3 ; 5720-05-8 ; 879-65-2 ; 98-96-4 ; 31519-62-7 ; 23688-89-3 ; 23611-75-8 ; 33332-25-1 ; 20737-42-2 ; 61442-38-4 ; 17933-03-8 ; 50681-25-9 ; 13924-99-7 ; 40155-43-9 ; 36070-80-1 ; 4595-61-3 ; 118853-60-4 ; 41110-28-5 ; 40155-42-8 ; 937669-80-2 ; 98-98-6 ; 31462-59-6 ; 16419-60-6 ; 5424-01-1 ; 59-67-6 ; 34604-60-9 ; 27398-39-6 ; 1196151-53-7 ; 19847-12-2 ; 13965-03-2 ; 876161-05-6 ; 27825-21-4 ; 2164-61-6 ; 4604-72-2 ; 98-97-5 ; 24005-61-6 ; 103-67-3 ; 5521-61-9 ; 2516-34-9 ; 2719-27-9 ; 123-90-0 ; 6761-50-8 ; 625-43-4 ; 872-64-0 ; 36932-49-7 ; 1528085-68-8 ; 1195533-51-7 ; 13534-79-7
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CAS No. : | 98-98-6 |
Formula : | C6H5NO2 |
M.W : | 123.10 |
SMILES Code : | O=C(O)C1=NC=CC=C1 |
Synonyms : |
PCL 016
|
MDL No. : | MFCD00006293 |
InChI Key : | SIOXPEMLGUPBBT-UHFFFAOYSA-N |
Pubchem ID : | 1018 |
GHS Pictogram: | ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H318 |
Precautionary Statements: | P264-P270-P280-P305+P351+P338-P310-P330-P403-P501 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.2 |
TPSA ? Topological Polar Surface Area: Calculated from | 50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 0.74 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 0.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 0.78 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -1.13 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 0.75 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.37 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.48 |
Solubility | 4.04 mg/ml ; 0.0328 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.35 |
Solubility | 5.47 mg/ml ; 0.0444 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -1.35 |
Solubility | 5.46 mg/ml ; 0.0444 mol/l |
Class? Solubility class: Log S scale | Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg | High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg | Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) | No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) | No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) | No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) | No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.54 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from | 0.0 |
Ghose? Ghose filter: implemented from | None |
Veber? Veber (GSK) filter: implemented from | 0.0 |
Egan? Egan (Pharmacia) filter: implemented from | 0.0 |
Muegge? Muegge (Bayer) filter: implemented from | 1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat | 0.56 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from | No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 1.04 |
* 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 |
---|---|---|
66% | A solution of 2,2,6,6-tetramethylpiperidine (8.48 g, 60 mmol) in tetrahydrofuran (100 mL)Cooling to -78 deg C, N-butyllithium (2.5 mol / L, 16 mL, 40 mmol) was added dropwise, Slowly warmed to room temperature for 30 minutes. Cooling to -78 deg C, This was added dropwise to a suspension of pyridine-2-carboxylic acid (2.46 g, 20 mmol) in tetrahydrofuran, After completion of the dropwise addition, the reaction was allowed to proceed at room temperature for 30 minutes, Cooling to -30 deg C, A solution of iodine (15.23 g, 60 mmol) in tetrahydrofuran was added dropwise to the reaction flask, The mixture was stirred at room temperature for 1 hour, add water, Standing overnight Precipitation of solids, The target compound was filtered (3.3 g, yield 66percent). | |
41% | Description 1; 3-Iodo-2-pyridinecarboxylic acid (D1); To a stirred solution of 2,2,6,6-tetramethylpiperidine (20 ml, 0.122 mol) in dry THF (100 ml) at -78° C., under argon was added n-butyllithium (52 ml, 0.163 mol, 2.5M solution in hexanes) dropwise, followed 15 min later by a solution of 2-pyridinecarboxylic acid (5.0 g, 0.0407 mol) in dry THF (30 ml). After 10 min at -78° C., the reaction mixture was warmed to 0° C. for 30 min. and then transferred to a solution of iodine (30.9 g, 0.243 mol) in dry THF (70 ml) at 0° C., under argon. After 15 min at 0° C. the reaction mixture was warmed to 25° C. and stirred for 1 h. After this period water (80 ml) was added and the reaction mixture concentrated in vacuo. The residue was re-dissolved in water (100 ml) and washed with EtOAc (100 ml). The aqueous layer was separated, concentrated in vacuo and the resulting residue triturated with diethyl ether. The solid material was filtered and dried in vacuo before being re-dissolved in MeOH (200 ml). To this solution was added Amberlyte IR-120 ion-exchange resin (100 g) and the reaction mixture stirred at 25° C. for 2 h. After this period the resin was filtered off and the solvents concentrated in vacuo to afford the title compound (4.15 g, 41percent). deltaH (DMSO-d6, 250 MHz) 6.79 (1H, bs) 7.28 (1H, dd), 8.37 (1H, dd), 8.58 (1H, dd). MS (ES): C6H41NO2 requires 249. found (M-H+) 248. | |
41% | Description 1; 3-lodo-2-pyridinecarboxylic acid (D1);To a stirred solution of 2,2,6,6-tetramethylpiperidine (20ml, 0.122mol) in dry THF (100ml) at -78 °C, under argon was added /7-butyllithium (52ml, 0.163mol, 2.5M EPO <DP n="40"/>solution in hexanes) dropwise, followed 15min later by a solution of 2- pyridinecarboxylic acid (5.Og, 0.0407mol) in dry THF (30ml). After 10min at -78 0C, the reaction mixture was warmed to 00C for 30 min. and then transferred to a solution of iodine (30.9g, 0.243mol) in dry THF (70ml) at 00C, under argon. After 15min at O0C the reaction mixture was warmed to 25°C and stirred for 1h. After this period water (80ml) was added and the reaction mixture concentrated in vacuo. The residue was re-dissolved in water (100ml) and washed with EtOAc (100ml). The aqueous layer was separated, concentrated in vacuo and the resulting residue triturated with diethyl ether. The solid material was filtered and dried in vacuo before being re- dissolved in MeOH (200ml). To this solution was added Amberlyte IR-120 ion- exchange resin (100g) and the reaction mixture stirred at 25°C for 2h. After this period the resin was filtered off and the solvents concentrated in vacuo to afford the title compound (4.15g, 41percent). deltaH (DMSO-d6, 250MHz) 6.79 (1H, bs) 7.28 (1H, dd), 8.37 (1 H, dd), 8.58 (1H, dd). MS (ES): C6H4INO2 requires 249; found (M-H+) 248. |
Example 503-[4-Chloro-3-[[(2-tricyclo[3.3.1.13'7]dec-l-ylethyl)amino]carbonyl]phenyl]-2-pyridinecarboxylic acidCIa) 3-Iodo-2-pyridinecarboxylic acid, methyl esterButyllithium (32 mL, 2.5 M in hexanes) was added dropwise over 10 minutes to a solutionof 2,2,6,6-tetramethylpiperidine (10.2 mL) in tetrahydrofuran (100 mL) at-7 8 °C undernitrogen. The mixture was stirred at -78 °C for 15 minutes and then picolinic acid (2.4 g)was added portionwise over 10 minutes. After a further 10 minutes at -78 °C the mixturewas allowed to warm to 0 °C and stirred under nitrogen for 30 minutes. The reactionmixture was then added dropwise over 15 minutes to a solution of iodine (15 g) intetrahydrofuran (100 mL) at 0 °C. This was then allowed to warm to room temperature andstirred for 1 hour before water (20 mL) was added. The mixture was evaporated to drynessto leave a black oil. Dichloromethane (50 mL) was added and the mixture was cooled to 0°C. A^JV-Dimethylformamide (1 drop) and oxalyl chloride (4 mL) were added. The reactionwas allowed to warm to room temperature and stirred under nitrogen for 2 hours, thenevaporated to dryness. The residue was dissolved hi dichloromethane (20 mL) and thenmethanol (20 mL) was added. The mixture was then stirred for 10 minutes before beingevaporated to afford the sub-title compound as an oil (1.0 g) which was used in the nextstep without purification.MS: APCI(+ve) 264 (M+H4"). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | General procedure: [00161] General method G: Mixed anhydride method for the synthesis of aromatic/hetero aromatic esters (41-44): 2-Methyl-6-nitrobenzoic anhydride (0.39 mmol) was added to a solution of pyridinecaboxylic acid (0.386 mmol) and DMAP (0.29 mmol) in THF (1 ml), and the resulting mixture was allowed to stand at room temperature for 5min. A solution of 5 (0.193 mmol) in THF (1 ml) was mixed with the above reagent mixture and then with TEA (0.1 ml). This reaction mixture was allowed to stand at room temperature for 2 h. Reaction mixture absorbed on silica and purified by FCC using 2percent ethanol in DCM in presence of traces of TEA (0.06percent). The picolinoyl, nicotinoyl, isonoctinoyl and 1,3-phenyldiacetic acid esters derivatives were synthesized in a manner similar to the above. TLC and 1H NMR and HRMS analyses revealed that the presence of other esters derived from 2-methyl-6-nitrobenzoic anhydride is absent. [00162] 3y9-(Pyridine-2-carboxylate)-17-(lH-benzimidazol-l-yl)-androsta-5,16-diene (41) : Compound 41 prepared by following general method G, using 2-Methyl-6-nitrobenzoic anhydride (0.13 g, 0.39 mmol), picolinic acid (0.05 g, 0.39 mmol), 4-DMAP (0.04 g, 0.29 mmol), THF (1 ml), 5 (0.075 g, 0.19 mmol), THF (1 ml) and TEA (0.1 ml). FCC gave pure 41 (0.09 g, 90percent): mp 243-44 °C; IR (Neat) 2942, 2852, 1729, 1496, 1286, 1227, 1139, 754 cm"1; 1H NMR (400 MHz, CDC13) delta 1.03 (s, 3 H, 18-CH3), 1.12 (s, 3 H, 19-CH3), 4.99 (m, 1 H, 3a-H), 5.49 (t, 1 H, J = 1.98 Hz, 6-H), 5.99 (t, 1 H, J = 1.42 Hz, 16-H), 7.32 (m, 2 H, aromatic-Hs), 7.46-7.50 (m, 2 H, picolinoyl-5-H and aromatic-H), 7.80-7.84 (m, 1 H, aromatic- H), and (1H, picolinoyl-4-H), 7.96 (s, 1 H, 2'-H), 8.15 (br, 1 H, picolinoyl-3-H), 8.79 (m, 1 H, picolinoyl-6- H); 13C NMR (500 MHz, CDC13) delta 164.9, 150.1, 148.7, 143.4, 141.8, 140.2, 137.2, 134.7, 127.0, 125.4, 124.4, 123.6, 122.7, 120.3, 111.4, 75.6, 56.0, 50.6, 47.4, 38.2, 37.2, 35.0, 31.3, 30.5, 27.8, 20.82, 19.5, 17.0. HRMS calcd 516.2621 (C32H3502N3.Na+), found 516.2614. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | HATU (116 mg, 0.305 mmol) was added to picolinic acid (37.5 mg, 0.305 mmol) and DIPEA (66 mu, 0.381 mmol) in DMF (2 ml). After 15 min, <strong>[369-26-6]methyl 3-amino-4-fluorobenzoate</strong> (43 mg, 0.254 mmol) in DMF (1 ml) was added. The mixture was stirred at ambient temperature for 10 d before solvent was evaporated and residue dissolved in EtOAc. The solution was washed with sat. NaHC03, dried (MgS04) and evaporated. Half of the crude material from above (0.127 mmol) was dissolved in dioxane (1.5 ml) and MeCN (1.5 ml). Potassium carbonate (35 mg, 0.254 mmol) was added and the mixture was heated at 180 °C for 2 h in a microwave reactor. Silica gel was added and solvents evaporated. The dry silica was applied on a flash column which was eluted with 35-50percent) EtOAc in hexanes. Yield: 6 mg (18percent>); colourless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; at 0 - 20℃; for 22h; | The detailed preparation for the picolinamide-modified beta-cyclodextrin/Pd(II) complex (Pd(II)PCA-beta-CD) is illustrated in Scheme 1. First, mono-6-tosyl beta-cyclodextrin (1, Tos-beta-CD) was obtained by the method of Khan etc (Khan & Pitchumani, 2016). Then, Tos-beta-CD was reacted with NaN3 to form 6-monodeoxy-6-monoazido-beta-CD (2, N3-beta-CD), which was further reduced by triphenylphosphine to give a key intermediate: 6-monodeoxy-6-amino-beta-CD (3). PCA-beta-CD (4) was prepared by condensation of PCA (2-pyridinecarboxylic acid) with NH2-beta-CD using N,N?-dicyclohexylcarbo-diimide (DCC) and 1-hydroxy-1H-benzotriazole (HOBt) in N,N?-dimethylformamide (DMF). The synthesis of PCA-(CH2)nNH-beta-CD (6) was achieved in two simple steps: nucleophilic substitution (from 1 to 5) and amidation (from 5 to 6). Finally, all the obtained ligands were stirred with Pd(OAc)2 at room temperature for 24 h in toluene, and the target complexes Pd(II)PCA-beta-CDs (C1-C3) were obtained as light yellow powders. The water solubility of the 4, 6 ligands and C1, C2, C3 complexes in different temperatures were studied. The results showed the complexes have high solubility in the aqueous solution (see Table 1S in SI). Reaction conditions: (a) TsCl, NaOH, CH3CN, H2O, rt, 2h, 15percent yield; (b) NaN3, DMF, 80°C, 12h, 93percent yield; (c) PPh3, DMF, rt, 10h, 91percent yield; (d) DCC, HOBt, DMF, 4h at 0°C, 18h at rt, 72?83percent yield; (e) Pd(OAc)2, toluene, rt, 24h, 60?70percent yield; (f) diamine, 80°C, 12h, 30percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.1% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl acetamide; at 80℃; for 2.0h; | Theta268] A solution of <strong>[50593-30-1]2-methyl-2H-indazol-6-amine</strong> (550 mg, 3.74 mmol), picolinic acid (690 mg, 5.61 mmol) and HATU (2.131 g, 5.61 mmol) in DMA (7.474 mL) was treated with DIPEA (1.953 mL, 11.21 mmol). The reaction mixture was stirred at 80C for 2 hours and then diluted with water (20 mL), Sodium chloride (3 g) was added and the mixture was stirred overnight and the resulting precipitate was filtered and dried in vacuum at 80C to give the title compound as a gray solid (340 mg, 36.1%). 1 1 NMR (400 MHz, DMSO-ae) delta ppm 4.14 (s, 3 l i s. 7.45 (dd, J=8.84, 1.77 Hz, 1H), 7.64 - 7.71 (m, 2 H), 8,09 (id,./ 7.7 1. 1.77 Hz, 1H), 8.19 (dt, J=7.83, 1.01Hz, 1H), 8.27 (s, 1H), 8.31 (s, 1H), 8,76 (d,,7=4.79 Hz, 1H), 10.61 (s, 1H); ESI-MS m/z |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 50℃; for 2.0h; | A mixture of picolinic acid (338 mg, 2.75 mmol), pyridine-3, 5-diamine (300 mg, 2.75 mmol) and EDCI.HC1 (580 mg, 3.02 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. LCMS (Rt = 0.329 min; MS Calcd: 214.1; MS Found: 214.9 [M+H]+). The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL x2), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give N-(5-aminopyridin-3-yl)picolinamide (400 mg, yield: 61%) as a light yellow solid. (1416) NMR (400 MHz DMSO-rie) d 5.39 (2H, brs), 7.64 (1H, t, J= 2.3 Hz), 7.67-7.72 (2H, m), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Into a 250-mL round-bottom flask was placed pyridine-2-carboxylic acid (9.8 g, 79 mmol), N,N-dimethylformamide (100 mL), N-(3 -dimethylaminopropyl)-N-ethyl carbodiimide hydrochloride (25.4 g, 132 mmol), 1-hydroxybenzotriazole hydrate (17.9 g, 132 mmol), and N,N-diisopropylethylamine (46 mL, 265 mmol). The resulting solution was stirred for 20 min at room temperature. To the mixture was added (S)-1-(3-methoxyphenyl)ethan-1-amine (10 g, 66 mmol), and the mixture was stirred overnight at room temperature. The reaction was diluted with ethyl acetate (400 mL). The resulting mixture was washed with brine (3 xlOO ml). The organics were concentrated, and the residue was purified on a silica gel column eluting with ethyl acetate/petroleum ether (1 :2) to yield (S)-N-(1-(3-methoxyphenyl)ethyl)picolinamide (12 g, 71%). |
Tags: 98-98-6 synthesis path| 98-98-6 SDS| 98-98-6 COA| 98-98-6 purity| 98-98-6 application| 98-98-6 NMR| 98-98-6 COA| 98-98-6 structure
A405225 [177359-60-3]
5-Methylpicolinic acid hydrochloride
Similarity: 0.92
A120787 [39977-41-8]
5-(Hydroxymethyl)picolinic acid
Similarity: 0.88
A137131 [934-60-1]
6-Methyl-2-pyridinecarboxylic acid
Similarity: 0.88
A183920 [502509-10-6]
4-(2-Hydroxyethyl)picolinic acid
Similarity: 0.88
A405225 [177359-60-3]
5-Methylpicolinic acid hydrochloride
Similarity: 0.92
A120787 [39977-41-8]
5-(Hydroxymethyl)picolinic acid
Similarity: 0.88
A137131 [934-60-1]
6-Methyl-2-pyridinecarboxylic acid
Similarity: 0.88
A183920 [502509-10-6]
4-(2-Hydroxyethyl)picolinic acid
Similarity: 0.88
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H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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