Category: 10242-03-2

Melzer, Marvin S. published the artcileApplicability of the Hammett equation to the indole system: acidity of indole-3-carboxylic acids, SDS of cas: 10242-03-2, the publication is Journal of Organic Chemistry (1962), 496-9, database is CAplus.

The acidities of six 5- and 6-substituted indole-3-carboxylic acids were determined in aqueous alc. and their pK plotted against the Hammett substituent constants of the resp. substituents. A good correlation was obtained using the one-term Hammett equation (log K/K° = ρσ) using σ_m for groups in the 5-position and σ_p for groups in the 6-position. These results were taken to indicate thai electronic effects were transmitted to the acid center through the C pare to the 6-position and that virtually no transmission occurred through the indole N atom. It was also found that the 5-bromoindole-3-carboxylic acid (I) was somewhat less acidic than expected, an effect attributed to steric and electronic factors. Infrared data indicated that whereas the 6-aminoindole-3-carboxylic acid (II) existed as the free acid, the 5-amino isomer (III) existed in its zwitterionic form. All pK measurements were made in 50% and 95% alc. and the pH measured using a Beckmann meter. Indole treated with MeMgI then CO₂ gave indote-3-carboxylic acid (IV), m. 214° (decomposition). 5-Nitroindote (.5 g.) treated 1 day in a refrigerator with excess (COCl)₂ gave 5 g. 5-nitroindole-3-glyoxylyl chloride (V), m. 310° (decomposition). V refluxed with KOH gave 3.5 g. 5-nitroindole 3-carboxylic acid (VI), m. 270-2° (decomposition). VI (3.5 g.) refluxed 3 hrs. in refluxing 30% H₂O₂, filtered hot, and the solid further purified gave 2.5 g. 5-nitroindole-3-carboxylic acid (VII), m. 276-8° (decomposition). A portion of V treated directly with 30% H₂O₂ gave 47% VII. V failed to undergo decarboxylation in refluxing tetrachloroethane. VII failed to undergo cleavage on treatment with Pb(OAc)₄ in refluxing AcOH. 5-Bromoindole treated with MeMgl and carbonated gave I, m. 238-40° (decomposition). IV in AcOH treated with HNO₃ gave 6-nitroimtole-3-carboxylic acid (VIII), m. 280-1°. Reduction of VIII in MeOH with Raney Ni under 35 lb./sq. in. H pressure gave II. Another preparation using the same procedure gave a small amount of material, m. 197-9°. VI (500 mg.) in MeOH shaken 8 hrs. with Raney Ni under 50 lb./sq. in. H pressure gave 65 mg. III, m. 177-9° (decomposition). The pK of indole-3-carboxylic acids at 26° were obtained (compound, pK in 50% alc., number of determinations, pK in 95% alc., no of determinations, a used, NH (cm.^-1 given): IV, 7.00, 9, 8.92, 3, 0.00, 3247; VIII, 6.45, 3, 8.06, 2, 0.78, 8425; VI, 6.50, 6, 8.15, 3, 0.71, 3338; I, 6.96, 7, 8.72, 3, 0.391, 3310; 5-ethoxyindote-3-carboxylic acid, 6.98, 6, 8.91, 2, 0.10, 3226; II, 7.43, 2, -, -, -0.66, 3312. Reaction constants and precision of correlation of pK of indole-3-carboxylic acids with Hammett substituent constants were given in a table.

Journal of Organic Chemistry published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, SDS of cas: 10242-03-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Bowden, Keith published the artcileThe transmission of polar effects. IV. The kinetics of esterification with diazodiphenylmethane of substituted heterocyclic carboxylic acids, Safety of 6-Nitro-1H-indole-3-carboxylic acid, the publication is Canadian Journal of Chemistry (1966), 44(13), 1493-9, database is CAplus.

cf. CA 64, 12480h. The rate coefficients for the reaction with diazodiphenylmethane, in EtOH at 30.0°, of a number of substituted indole-2-carboxylic acids, indole-3-carboxylic acids, coumarin-3-carboxylic acids, coumarilic acids, and N-phenylglycines have been determined The effect of substitution is assessed by use of adapted Hammett and Dewar-Grisdale relations. The relations give good correlations for oxygen-ring heterocyclic systems, and the relative ability of the systems to transmit π-electron effects has been determined An anomalous perturbing effect appears to operate in the indolecarboxylic acid systems.

Canadian Journal of Chemistry published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, Safety of 6-Nitro-1H-indole-3-carboxylic acid.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Elkin, Samuel published the artcileSynthesis and local anesthetic activity of several dialkylaminoalkyl esters of indolecarboxylic acids, Category: indole-building-block, the publication is Journal of Pharmaceutical Sciences (1963), 79-81, database is CAplus.

By the method of Burtner and Cusic (CA 37, 1711³), compounds having the general formulas I and II were prepared (compound, R, n, % yield, and m.p. given): I, H, 2, 25, 174-5°; I, H, 3, 21.8, 165-7°; I, NO₂, 2, 15.6, 210-12°; I, NO₂, 3, 15.1, 208-10°; II, –, 2, 6.2, 178-80°; II, –, 3, 17.5, 170-1°. All compounds were effective as topical anesthetics but had no action on unbroken skin. Nitrated indole-3-carboxylic acid and the esters of indole-2-carboxylic acid showed a marked decrease in duration of local anesthetic activity.

Journal of Pharmaceutical Sciences published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, Category: indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wen, Hui published the artcileDesign and synthesis of indoleamine 2,3- Dioxygenase 1 inhibitors and evaluation of their use as anti-tumor agents, Application of 6-Nitro-1H-indole-3-carboxylic acid, the publication is Molecules (2019), 24(11), 2124, database is CAplus and MEDLINE.

Indoleamine 2,3-dioxygenase (IDO) 1 is the key enzyme for regulating tryptophan metabolism and is an important target for interrupting tumor immune escape. In this study, we designed four series of compounds as potential IDO1 inhibitors by attaching various fragments or ligands to indole or phenylimidazole scaffolds to improve binding to IDO1. The compounds were synthesized and their inhibitory activities against IDO1 and tryptophan 2,3-dioxygenase were evaluated. Two compounds with a phenylimidazole scaffold (DX-03-12 and DX-03-13) showed potent IDO1 inhibition with IC₅₀ values of 0.3-0.5μM. These two IDO1 inhibitors showed low cell cytotoxicity, which indicated that they may exert their anti-tumor effect via immune modulation. Compound DX-03-12 was investigated further by determining the in vivo pharmacokinetic profile and anti-tumor efficacy. The pharmacokinetic study revealed that DX-03-12 had satisfactory properties in mice, with rapid absorption, moderate plasma clearance (~36% of hepatic blood flow), acceptable half-life (~4.6 h), and high oral bioavailability (~96%). Daily oral administration of 60 mg/kg of compound DX-03-12 decreased tumor growth by 72.2% after 19 days in a mouse melanoma cell B16-F10 xenograft model compared with the untreated control. Moreover, there was no obvious weight loss in DX-03-12-treated mice. In conclusion, compound DX-03-12 is a potent lead compound for developing IDO1 inhibitors and anti-tumor agents.

Molecules published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C8H14O2, Application of 6-Nitro-1H-indole-3-carboxylic acid.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Martin, James S. published the artcileSynthesis of a Series of Diaminoindoles, HPLC of Formula: 10242-03-2, the publication is Journal of Organic Chemistry (2021), 86(17), 11333-11340, database is CAplus and MEDLINE.

A selection of 3,4-diaminoindoles were required for a recent drug discovery project. To this end, a 10-step synthesis was developed from 4-nitroindole. This synthesis was subsequently adapted and used to synthesize 3,5-; 3,6-; and 3,7-diaminoindoles from the corresponding 5-, 6-, or 7-nitroindole. These novel intermediates feature orthogonal protecting groups that allow them to be further diversified. This is the first reported synthesis of these types of compounds

Journal of Organic Chemistry published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, HPLC of Formula: 10242-03-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Bert, Giancarlo published the artcileThe nitration of 3-indolecarboxyaldehyde and ethyl 3-indoleglyoxylate, HPLC of Formula: 10242-03-2, the publication is Gazzetta Chimica Italiana (1961), 728-41, database is CAplus.

A suspension of 1 g. 3-indolecarboxaldehyde (I) in 8 ml. AcOH treated with 1.05 ml. HNO₃ (d. 1.37), heated to 80° until an exothermic reaction began, and cooled rapidly gave 0.2 g. 6-nitro-3-indolecarboxaldehyde (II), m. 302-4° (Me₂CO-EtOH). A solution of 5.7 g. KNO₃ in 10 ml. H₂SO₄ was added slowly at 10° to 5 g. I in 15 ml. concentrated H₂SO₄, the mixture stirred 10 min., poured onto ice, and the precipitate extracted with 100 ml. boiling C₆H₆ to yield 5.5 g. mixture, which was shown by spectrophotometric analysis to consist of 34% II and 66% 5-nitro-3-indolecarboxaldehyde (III), m. 300-2°; fractional crystallization from EtOH allowed partial separation of the two compounds A solution of 0.35 g. II in 10 ml. EtOH and 1 ml. 2N NaOH was boiled 15 min. with 0.25 g. KBH₄, cooled, acidified, and extracted with Et₂O; the residue of the evaporation of the Et₂O was extracted with ligroine to give 5 mg. yellow needles (6-nitroskatole ?), m. 122-4°; the ligroineinsol. part yielded after extraction with C₆H₆ 25 mg. 3-hydroxymethyl-6-nitroindole (IV), m. 144-6° (decomposition). Oxidation of 0.2 g. II in 1 ml. 2N NaOH by refluxing 1 hr. with 0.54 g. AgNO₃ in 10 ml. 2N NH₃ gave 60 mg. 6-nitro-3-indolecarboxylic acid (V), m. 265-7°; the same result was obtained with alk. KMnO₄; similarly the mixture of II and III gave a mixture, m. 225-30°, of V and 5-nitro-3-indolecarboxylic acid (VI). V and VI were transformed resp. into 6- and 5-nitroindole by heating at 160-80° in quinoline. A suspension of 1 g. ethyl 3-indoleglyoxylate (VII) in 8 ml. AcOH heated 30 min. at 80° with 0.8 ml. HNO₃ (d. 1.37) gave 0.4 g. ethyl 6-nitro-3-indolecarboxylate (VIII), m. 284-6° (decomposition) (EtOH), while 0.11 g. 4-nitro-3-indoleglyoxylate, m. 184-6° (EtOH), was obtained by concentration of the mother liquor. Nitration of 4 g. VII in 28 ml. concentrated H₂SO₄ with 2.8 g. KNO₃ led to 3.3 g. mixture of 34% VIII and 66% ethyl 5-nitro-3-indoleglyoxylate (IX), m. 280-2° (decomposition), which was separated in part by crystallization from Me₂CO. Saponification of VIII with KOH in EtOH gave the free acid (X), decomposing above 250° (Me₂NCHO-H₂O); similarly, IX yielded 5-nitro-3-indolecarboxylic acid (XI), decomposing at 233° (Me₂NCHO-H₂O). X and XI were decarboxylated to II and III at 170-80° in quinoline. Ultraviolet curves were given for I, II, III, IV, VIII, and IX.

Gazzetta Chimica Italiana published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, HPLC of Formula: 10242-03-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Majima, Riko published the artcileSynthetic experiments in the indole group. VII. Nitration and bromination of β-indolecarboxylic ester and a new synthesis of the dye of the purple of antiquity, Computed Properties of 10242-03-2, the publication is Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen (1930), 2237-45, database is CAplus.

cf. C. A. 20, 758. A repetition of the work of Oddo and Sessa (C. A. 5, 2638) not only confirmed the earlier observation that, contrary to the statements of O. and S., Et β-indolecarboxylate (I) is formed by the action of ClCO₂Et on indolylmagnesium iodide but also showed that di-Et N, β-indoledicarboxylate (II) is formed at the same time; to obtain II in good yield it is well to use 2 mols. ClCO₂Et per mol. of indole. Addition of concentrated HNO₃ to I in cold AcOH gives chiefly Et 6-nitroindole-3-carboxylate (III), saponified by KOH to the free and (IV) which with hot quinoline gives 6-nitroindole (V). The position of the NO₂ group was established by oxidation of the salt of IV with aqueous KMnO₄ to 2,4-H₂N(O₂N)C₆H₃-CO₂H. With HCl and SnCl₂ in AcOH III readily yields the 3-amino ester (VI). V similarly gives the amorphous and very unstable 6-aminoindole (VII). I is readily brominated in AcOH, giving chiefly either Et 6-bromoindole-3-carboxylate (VIII) or the 5,6-di-Br ester (IX), depending on the conditions. The free di-Br acid (X) can be further converted into 5,6-dibromoindole (XI). X with CrO₃ in AcOH gives a red 5,6-dibromoisatin (XII), m. above 290°, which on distillation with KOH yields a Br₂C₆H₃NH₂, m. 79-80° (of the known Br₂C₆H₃NH₂, the 3,4-compound, m. 80.4°, comes closest in its properties to the one obtained from XII). XII on further oxidation with CrO₃ in AcOH gives a dibromoisatoic acid (XIII) which with concentrated HCl yields 4,5,2-Br₂(H₂N)C₆H₂CO₂H, m. 227-8°. In the same way VIII gave 6-bromoisatin (XIV), different from Borsche and Jacobs’ synthetic 5-Br compound With 03 in alk. solution, VIII readily gives 6,6′-dibromoindigo (XV), thus further confirming the structure of VIII. II (1.1 g. from 3 g. indole through the Mg compound with 2 mols. ClCO₂Et), less soluble in alc. than I, m. 102-3°. The yield of I has been increased to over 78% by slowly adding 11 g. ClCO₂Et to the Mg derivative from 11 g. indole in cold Et₂O. III, light yellowish needles, m. 198-9°. IV, yellow, becomes opaque at 227°, decomposes around 275-8°; its alkali salts dissolve in H₂O with orange-red color. V, yellow, m. 139-40.5°. VI, m. 149-50°; HCl salt; chloroplatinate. β-Indolealdehyde in AcOH with HNO₃ (d. 1.4) gives an addition product, C₉H₇ON.HNO₃, decomposes 94°; with excess of HNO₃ on the H₂O bath is obtained a nitro-β-indolealdehyde, light yellow, m. around 290° (decomposition), turns brownish in the air. VIII, m. 134-7°; free acid, m. 212°. IX (85% from 2 g. I and 4 g. Br), m. 223-5°. X, m. 255-7°; if, in the saponification of IX, the boiling with excess of ale. KOH is continued 10 hrs. the product is XI, m. 154°. XII, m. 290°, shows the indopbenin reaction, gives with dilute NaOH a dark violet precipitate which redissolves with yellow color on heating and acids reppt. the original XII. XIV, orange-red, m. 256-8°. 5,5′,6,6′-Tetrabrornoindigo, is obtained from IX with O₃; it dyes silk in somewhat less reddish shades than XV, the chief constituent of the purple of the ancients.

Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, Computed Properties of 10242-03-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Jiang, Fanwei published the artcileSynthesis of substituted indole-3-carboxylic acid derivatives, Category: indole-building-block, the publication is Huaxue Tongbao (2015), 78(4), 378-380, database is CAplus.

Indole-3-carboxylic acid was a kind of important organic intermediate, which could be widely used in the synthesis of medicine and pesticide. Substituted 2-nitro-β-dimethylamino styrene was obtained from the reaction of substituted 2-nitrotoluene and N,N-dimethylformamide di-Me acetal in N,N-dimethylformamide, which was further reacted with iron and acetic acid to give substituted indoles. Five substituted indole-3-carboxylic acids were synthesized from substituted indoles and trifluoroacetic anhydride. The reported synthesis had the advantages of simple post treatment, mild conditions and higher yields.

Huaxue Tongbao published new progress about 10242-03-2. 10242-03-2 belongs to indole-building-block, auxiliary class Indole,Nitro Compound,Carboxylic acid,Indole, name is 6-Nitro-1H-indole-3-carboxylic acid, and the molecular formula is C9H6N2O4, Category: indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles