Tag: M.W=200-250

Davies, Huw M. L. published the artcileC-H Activation as a Strategic Reaction: Enantioselective Synthesis of 4-Substituted Indoles, Category: indole-building-block, the publication is Journal of the American Chemical Society (2006), 128(4), 1060-1061, database is CAplus and MEDLINE.

A method is described for the asym. synthesis of 4-substituted indoles, e.g., I, from the Rh₂(S-DOSP)₄-catalyzed decomposition of vinyldiazoacetates in the presence of N-Boc-4-acetoxy-6,7-dihydroindole. The reaction proceeds via a combined C-H activation/Cope rearrangement-elimination mechanism resulting in good yields and very high asym. induction. The absolute configuration of I was determined by X-ray crystallog. of its reduced analog.

Journal of the American Chemical Society published new progress about 27784-79-8. 27784-79-8 belongs to indole-building-block, auxiliary class Other Aromatic Heterocyclic,Bromide,Ketone, name is 2-Bromo-6,7-dihydro-1H-indol-4(5H)-one, and the molecular formula is C8H8BrNO, 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

Lim, Soobin published the artcileCobalt-Catalyzed C-F Bond Borylation of Aryl Fluorides, Product Details of C14H18BNO2, the publication is Organic Letters (2018), 20(22), 7249-7252, database is CAplus and MEDLINE.

A mild and practical Co-catalyzed defluoroborylation of fluoroarenes is presented for the 1st time. The method permits straightforward functionalization of fluoroarenes, with high selectivity for borylation of C-F over C-H bonds, and a tolerance for aerobic conditions. Also, two-step ¹⁸F-fluorination was achieved for expanding the scope of ¹⁸F-positron emission tomog. probes.

Organic Letters published new progress about 642494-36-8. 642494-36-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Indole,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H18BNO2, Product Details of C14H18BNO2.

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

Blaikie, K. G. published the artcileMethoxyindoles and their derivatives, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Journal of the Chemical Society, Transactions (1924), 296-335, database is CAplus.

2,5-O₂N(HO)C₆H₃Me, m. 128°, was obtained in 58 g. yield (together with 42 g. of 4,5-O₂N(HO)C₆H₃Me) by slowly adding 140 g. m-HOC₆H₄Me in 140 g. AcOH to a stirred mixture of 200 g. HNO₃ (d. 1.5) and 400 g. AcOH at -8° to -5°, and removing the 4-NO₂ derivative by steam distillation Me₂SO₄ (252 g.) added to 153 g. 2,5-O₂N(HO)C₆H₃Me and 46 g. Na in 750 cc. MeOH gave a 90% yield of 2,5-O₂N(MeO)C₆H₃Me (I), m. 55°. 2-Nitro-5-methoxyphenylpyruvic acid (II), yellow, m. 128° (phenylhydrazone, yellow, m. 151-2° (decomposition)), results in 51 g. yield from 50 g. of I and 63 g. (CO₂Et)₂ added to a suspn. of 35 g. EtONa in 300 cc. dry Et₂O. Oxidation of II by H₂O₂ in 2% NaOH gave 2-nitro-5- methoxyphenylacetic acid, m. 176°. Reduction of II in NH₄OH by FeSO₄ gave a 73% yield of 5-methoxyindole-2-carboxylic acid (III), m. 196-7° (evolution of gas). Warmed with Ehrlich’s reagent, a deep pink color is produced, which fades on cooling. Me ester, m. 177°. Et ester, m. 156°. 2,3-O₂N(MeO)C₆H₃Me, (CO₂Et)₂ and KOEt in Et₂O give a 75% yield of 2-nitro-3-methoxy-phenylpyruvic acid (IV), pale yellow, m. 161-2°, or yellow with 0.5 AcOH of crystallization, m. 118-45°. The EtOH solution gives a deep green color with FeCl₃, destroyed by mineral acids. Phenylhydrazone, yellow, m. 159° (decomposition). Oxidation of IV gives 2-nitro-3-methoxyphenylacetic acid, m. 137-8°, while reduction with FeSO₄ and NH₄OH gives 7-methoxyindole-2-carboxylic acid (V), m. 182° and decomposes on continued heating. Et ester, m. 114°. Me ester, m. 120°. 2-Nitro-6-methoxyphenylpyruvic acid (VI), yellow, m. 47-55°; phenylhydrazone, yellow, m. 173-4° (decomposition). Oxidation with H₂O₂ gives 2-nitro-6-methoxyphenylacetic acid, yellow, m. 172°, while reduction of VI gave 4-methoxyindole-2-carboxylic acid (VII), m. 234-5°, in 63% yield. Ehrlich’s reagent gives a purple color, which disappears on cooling. Me ester, m. 143.5°. Et ester, m. 161.5°. p-MeOC₆H₄NHNH₂ (VIII), best prepared by diazotizing p-MeOC₆H₄NH₂ and reducing with SnCl₂ in concentrated HCl, m. 65°; yield, 44%. α-Ketobutyric acid p-methoxy-phenylhydrazone (IX), yellow, m. 105°. o-Methoxyphenylhydrazone (X), pale yellow, m. 112°. The action of concentrated H₂SO₄ on IX (or the components in EtOH) gives 5-methoxyskatole-2-carboxylic acid (XI), m. 200-1° (decomposition), isolated as the Et ester, m. 151-2°; Me ester, m. 156°. In the same way X gave 7-methoxyskatole-2-carboxylic acid (XII), m. 222-3°, isolated as the Me ester, m. 144-15°, the yield of the acid being only 23%. A by-product of this reaction is Et ketobutyrate phenylhydrazone, yellow, m. 59-60°. III, changed to the acid chloride by PCl₅ in AcCl, this dissolved in CHCl₃ and treated with MeNHCH₂CH(OMe)₂, gave 5-methoxyindole-2-carboxydimethylacetalyl-methylamide, m. 159°. This is converted by warming with saturated alc. HCl at 40-50° for 15 min. into a mixt, of about equal amounts of 10-methoxy-3-keto-4-methyl-3,4-dihydro-4-carboline (XIII), m. 280°, has a distinct blue fluorescence in the solid state, gives a yellow HCl salt, which is dissociated by H₂O and gives no color with Ehrlich’s reagent or with vanillin and HCl in the cold; the alc. solution has a striking lilac fluorescence; and 10- methoxy-5-keto-4- methyl-4,5-dihydroindole-1,4-diazine (XIV), m. 243°, gives a greenish blue color with Ehrlich’s reagent, fading to a pale yellow on cooling and becoming green on boiling, and gives an intense purple color with vanillin and HCl; the EtOH solution has a very faint blue fluorescence which is not increased by adding HCl. 5-Methoxyindole-2-carboxyacetalylamide m. 151-2°, results from the chloride of III and H₂NCH₂CH(OEt)₂; Ehrlich’s reagent gives a purple solution, becoming intense blue on warming, while NaNO₂ produces a green color in the cold. Vanillin and HCl produce a deep pink which becomes intense bluish violet on the addition of NaNO₂ and warming. The action of alc. HCl gives 10-methoxy-5-keto-4,5-dihydroindole-1,4-diazine (XV), sinters 265°, m. 280°. 5-Methoxyindole-2-carboxydimethylacetalylamide, m. 154°, and with alc. HCl gives XV. 5-Methoxyindole-2-carboxyacetalylmethylamide, m. 127°, is formed from the chloride of III and MeNHCH₂CH(OEt)₂; with alc. HCl it yields about equal quantities of XIII and XIV. 7- Methoxyindole-2-carboxydimethylacetalylmethylamide, obtained only as a sirup, gives with alc. HCl a mixture of approx. 4 parts 12-methoxy-3-keto-4-methyl-3,4-dihydro-4-carboline, pale yellow, m. 250°, yielding a golden-yellow HCl salt, and 1 part 12-methoxy-5-keto-4-methyl-4,5-dihydroindole-l,4-diazine, m. 135°, which gives a blue color with vanillin and HCl and a green color with Ehrlich’s solution 4-Methoxyindole-2-carboxydimethylacetalylmethylamide, m. 112°, which, with alc. HCl, gave 9-methoxy-3-keto-4-methyl-3,4-dihydro-4-carboline, m. 250°, and yields a sparingly soluble yellow HCl salt. The mother liquors gave a green color with vanillin and HCl but the diazine was not isolated. When XII was subjected to the above reactions, a compound C₁₄H₁₃O₂N₂Cl, m. 190°, was obtained, which was unchanged by treatment with 10% MeOH-KOH for 10 min. and is probably 9-chloro-12-methoxy-5-keto-4,7-dimethyl-4,5-dihydroindol-l,4-diazine. III decomposes vigorously when heated to 205-210°, yielding 5-methoxyindole (XVI), b₁₇ 176-8° m. 55°, acquires a pink tint which slowly darkens on standing, is only slightly volatile with steam (1 g. per l. of H₂O), colors a pine shaving moistened with HCl reddish violet, gives a purple precipitate with concentrated HNO₃ and NaNO₂. Picrate, bright red, m. 145°. 1-Ac derivative (XVII), b₂₅ 210-1°, m. 80-1°. Nitration of the Ac derivative gave a mixture of an a-NO₂ derivative, light brown, m. 149°, soluble in EtOH, and the b-NO₂ derivative, brown, m. 213-4°, the a-derivative predominating. Hydrolysis gave a- and b-nitro-5-methoxyindoles, yellow, m. 144° (mixture m. about 112°); the a-form gives an orange-purple color with a pine stick, the b-form a deep purple. The a-form gives a pale red color with Ehrlich’s reagent, not affected by addition of NaNO₂, while the b-form develops a red color only after addition of NaNO₂. XVI, treated with CHCl₃ and EtOH-KOH, yields a mixture of 5-methoxyindole-3-aldehyde, m. 178°, and 3-chloro-6-methoxyquinoline, m. 73-4°, separated by steam distillation XVI was also synthesized as follows: 4-Methoxy-2-aldehydophenylglycineamide oxime, yellow, m. 196° (decomposition) was obtained in 70% yield from 5,2-MeO(H₂N)C₆H₃CH:NOH and ClCH₂CONH₂ (formyl derivative, bright yellow, m. 223°); on hydrolysis yields 4-methoxy-2-aldehydophenylglycine oxime, pale yellow, m. 178°; with saturated H₂SO₃ this is changed to 4-methoxy-2-aldehydophenylglycine, bright orange, m. 183° (decomposition) (phenylhydrazone, yellow, m. 175-6°) which yields XVII on boiling with AC₂O and AcONa. V, decomposed at 230-3°, gives 73% of 7-methoxyindole, b₁₇ 157°, b₂₁ 159-61°, slowly turns brown on keeping, fairly volatile with steam (2 g. per 500 cc. H₂O), gives a deep mauve pine-shaving reaction, gives a yellow color with Ehrlich’s reagent, deepening to orange-red on warming and to a deep reddish purple on addition of dilute NaNO₂. Picrate, red, m. 156°. With alc. KOH and CHCl₃ this yields 7-methoxyindole-3-aldehyde, m. 159-60°, and 3-chloro-8-methoxyquinoline, m. 84.5°; the yield of both products was small. VII, at 245-50°, gives 4-methoxyindole, m. 69.5°, (picrate, red, m. 159-60°) gives a deep purple pine-shaving reaction and a reddish purple color with Ehrlich’s reagent. XI decomposes at 210° and gives 75% of 5-methoxyskatole, m. 66°, apparently non-volatile with steam, gives a red pine-shaving reaction and a reddish purple color with Ehrlich’s reagent. Picrate, dark red, m. 151-2°. XII similarly yields 7-methoxyskatole, b₂₀ 170° (picrate, brownish red, m. 156°). The pine-shaving reaction is a deep purplish red; Ehrlich’s reagent gives no color in the cold; on warming a reddish purple color develops. The K derivative of II gives with Me₂SO₄ 2-nitro-α-methoxycinnamic acid (XVIII), pale yellow, m. 164-5°. Na salt, yellow. Me ester, pale yellow, m. 67°; the Et ester appears to be an oil. Oxidation of XVIII gives o-O₂NC₆H₄CHO. Reduction of XVIII with FeSO₄ and NH₄OH gives the 2-amino derivative, pale yellow, crystallines with 2AcOH and m. 167°. Me ester, yellow, m. 60-1°. The acid readily loses MeOH, forming indole-2-carboxylic acid, m. 203-4° (heating above its m. p., solution in cold concentrated H₂SO₄ at room temperature for 16 hrs., boiling with 10% HCl or reduction of XVIII with FeSO₄ and NH₄OH and boiling the reaction product for 24 hrs.). 2-Nitro-α,3-dimethoxycinnamic acid, from IV, as above, m. 202° (decomposition), and reduced to the 2-amino derivative, m. 139°, and decomposing above its m. p. to give V.

Journal of the Chemical Society, Transactions published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate.

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

Londregan, Allyn T. published the artcileSynthesis of Pyridazine-Based α-Helix Mimetics, Recommanded Product: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is ACS Combinatorial Science (2016), 18(10), 651-654, database is CAplus and MEDLINE.

A versatile synthesis of pyridazine-based small mol. α-helix mimetics is presented. Modular C-C, C-N, and C-O bond-forming reactions allow for the inclusion of a variety of aliphatic, basic, aromatic, and heteroaromatic side chain moieties. This robust synthesis is suitable for the preparation of small pyridazine-based libraries.

ACS Combinatorial Science published new progress about 642494-36-8. 642494-36-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Indole,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H18BNO2, Recommanded Product: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

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

Zhang, Chufeng published the artcileDiscovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease, Synthetic Route of 166883-20-1, the publication is Journal of Medicinal Chemistry (2021), 64(4), 1966-1988, database is CAplus and MEDLINE.

The design, synthesis, and structure-activity relationships (SARs) of 3-(4-(2-((1H-indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile I [R⁵= 2-cyanoethyl; R⁶ = Me, fluoro; R⁷ = indolin-5-yl, 1-oxoisoindolin-5-yl, 1-tert-butoxycarbonylindol-5-yl, etc.] as selective TYK2 inhibitors was reported. Among them, compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] exhibited acceptable TYK2 inhibition with an IC₅₀ value of 9 nM, showed satisfactory selectivity characteristics over the other three homologous JAK kinases, and performed good functional potency in the JAK/STAT signaling pathway on lymphocyte lines and human whole blood. In liver microsomal assay studied that the clearance rate and half-life of I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] were 11.4 mL/min/g and 121.6 min, resp. Furthermore, in a dextran sulfate sodium colitis model, I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] reduced the production of pro-inflammatory cytokines IL-6 and TNF-α and improved the inflammation symptoms of mucosal infiltration, thickening, and edema. Compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] was aselective TYK2 inhibitor and was used to treat immune diseases and deserved further investigation.

Journal of Medicinal Chemistry published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C10H11NO4, Synthetic Route of 166883-20-1.

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

Blaikie, K. G. published the artcileMethoxyindoles and their derivatives, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Journal of the Chemical Society, Transactions (1924), 296-335, database is CAplus.

2,5-O₂N(HO)C₆H₃Me, m. 128°, was obtained in 58 g. yield (together with 42 g. of 4,5-O₂N(HO)C₆H₃Me) by slowly adding 140 g. m-HOC₆H₄Me in 140 g. AcOH to a stirred mixture of 200 g. HNO₃ (d. 1.5) and 400 g. AcOH at -8° to -5°, and removing the 4-NO₂ derivative by steam distillation Me₂SO₄ (252 g.) added to 153 g. 2,5-O₂N(HO)C₆H₃Me and 46 g. Na in 750 cc. MeOH gave a 90% yield of 2,5-O₂N(MeO)C₆H₃Me (I), m. 55°. 2-Nitro-5-methoxyphenylpyruvic acid (II), yellow, m. 128° (phenylhydrazone, yellow, m. 151-2° (decomposition)), results in 51 g. yield from 50 g. of I and 63 g. (CO₂Et)₂ added to a suspn. of 35 g. EtONa in 300 cc. dry Et₂O. Oxidation of II by H₂O₂ in 2% NaOH gave 2-nitro-5- methoxyphenylacetic acid, m. 176°. Reduction of II in NH₄OH by FeSO₄ gave a 73% yield of 5-methoxyindole-2-carboxylic acid (III), m. 196-7° (evolution of gas). Warmed with Ehrlich’s reagent, a deep pink color is produced, which fades on cooling. Me ester, m. 177°. Et ester, m. 156°. 2,3-O₂N(MeO)C₆H₃Me, (CO₂Et)₂ and KOEt in Et₂O give a 75% yield of 2-nitro-3-methoxy-phenylpyruvic acid (IV), pale yellow, m. 161-2°, or yellow with 0.5 AcOH of crystallization, m. 118-45°. The EtOH solution gives a deep green color with FeCl₃, destroyed by mineral acids. Phenylhydrazone, yellow, m. 159° (decomposition). Oxidation of IV gives 2-nitro-3-methoxyphenylacetic acid, m. 137-8°, while reduction with FeSO₄ and NH₄OH gives 7-methoxyindole-2-carboxylic acid (V), m. 182° and decomposes on continued heating. Et ester, m. 114°. Me ester, m. 120°. 2-Nitro-6-methoxyphenylpyruvic acid (VI), yellow, m. 47-55°; phenylhydrazone, yellow, m. 173-4° (decomposition). Oxidation with H₂O₂ gives 2-nitro-6-methoxyphenylacetic acid, yellow, m. 172°, while reduction of VI gave 4-methoxyindole-2-carboxylic acid (VII), m. 234-5°, in 63% yield. Ehrlich’s reagent gives a purple color, which disappears on cooling. Me ester, m. 143.5°. Et ester, m. 161.5°. p-MeOC₆H₄NHNH₂ (VIII), best prepared by diazotizing p-MeOC₆H₄NH₂ and reducing with SnCl₂ in concentrated HCl, m. 65°; yield, 44%. α-Ketobutyric acid p-methoxy-phenylhydrazone (IX), yellow, m. 105°. o-Methoxyphenylhydrazone (X), pale yellow, m. 112°. The action of concentrated H₂SO₄ on IX (or the components in EtOH) gives 5-methoxyskatole-2-carboxylic acid (XI), m. 200-1° (decomposition), isolated as the Et ester, m. 151-2°; Me ester, m. 156°. In the same way X gave 7-methoxyskatole-2-carboxylic acid (XII), m. 222-3°, isolated as the Me ester, m. 144-15°, the yield of the acid being only 23%. A by-product of this reaction is Et ketobutyrate phenylhydrazone, yellow, m. 59-60°. III, changed to the acid chloride by PCl₅ in AcCl, this dissolved in CHCl₃ and treated with MeNHCH₂CH(OMe)₂, gave 5-methoxyindole-2-carboxydimethylacetalyl-methylamide, m. 159°. This is converted by warming with saturated alc. HCl at 40-50° for 15 min. into a mixt, of about equal amounts of 10-methoxy-3-keto-4-methyl-3,4-dihydro-4-carboline (XIII), m. 280°, has a distinct blue fluorescence in the solid state, gives a yellow HCl salt, which is dissociated by H₂O and gives no color with Ehrlich’s reagent or with vanillin and HCl in the cold; the alc. solution has a striking lilac fluorescence; and 10- methoxy-5-keto-4- methyl-4,5-dihydroindole-1,4-diazine (XIV), m. 243°, gives a greenish blue color with Ehrlich’s reagent, fading to a pale yellow on cooling and becoming green on boiling, and gives an intense purple color with vanillin and HCl; the EtOH solution has a very faint blue fluorescence which is not increased by adding HCl. 5-Methoxyindole-2-carboxyacetalylamide m. 151-2°, results from the chloride of III and H₂NCH₂CH(OEt)₂; Ehrlich’s reagent gives a purple solution, becoming intense blue on warming, while NaNO₂ produces a green color in the cold. Vanillin and HCl produce a deep pink which becomes intense bluish violet on the addition of NaNO₂ and warming. The action of alc. HCl gives 10-methoxy-5-keto-4,5-dihydroindole-1,4-diazine (XV), sinters 265°, m. 280°. 5-Methoxyindole-2-carboxydimethylacetalylamide, m. 154°, and with alc. HCl gives XV. 5-Methoxyindole-2-carboxyacetalylmethylamide, m. 127°, is formed from the chloride of III and MeNHCH₂CH(OEt)₂; with alc. HCl it yields about equal quantities of XIII and XIV. 7- Methoxyindole-2-carboxydimethylacetalylmethylamide, obtained only as a sirup, gives with alc. HCl a mixture of approx. 4 parts 12-methoxy-3-keto-4-methyl-3,4-dihydro-4-carboline, pale yellow, m. 250°, yielding a golden-yellow HCl salt, and 1 part 12-methoxy-5-keto-4-methyl-4,5-dihydroindole-l,4-diazine, m. 135°, which gives a blue color with vanillin and HCl and a green color with Ehrlich’s solution 4-Methoxyindole-2-carboxydimethylacetalylmethylamide, m. 112°, which, with alc. HCl, gave 9-methoxy-3-keto-4-methyl-3,4-dihydro-4-carboline, m. 250°, and yields a sparingly soluble yellow HCl salt. The mother liquors gave a green color with vanillin and HCl but the diazine was not isolated. When XII was subjected to the above reactions, a compound C₁₄H₁₃O₂N₂Cl, m. 190°, was obtained, which was unchanged by treatment with 10% MeOH-KOH for 10 min. and is probably 9-chloro-12-methoxy-5-keto-4,7-dimethyl-4,5-dihydroindol-l,4-diazine. III decomposes vigorously when heated to 205-210°, yielding 5-methoxyindole (XVI), b₁₇ 176-8° m. 55°, acquires a pink tint which slowly darkens on standing, is only slightly volatile with steam (1 g. per l. of H₂O), colors a pine shaving moistened with HCl reddish violet, gives a purple precipitate with concentrated HNO₃ and NaNO₂. Picrate, bright red, m. 145°. 1-Ac derivative (XVII), b₂₅ 210-1°, m. 80-1°. Nitration of the Ac derivative gave a mixture of an a-NO₂ derivative, light brown, m. 149°, soluble in EtOH, and the b-NO₂ derivative, brown, m. 213-4°, the a-derivative predominating. Hydrolysis gave a- and b-nitro-5-methoxyindoles, yellow, m. 144° (mixture m. about 112°); the a-form gives an orange-purple color with a pine stick, the b-form a deep purple. The a-form gives a pale red color with Ehrlich’s reagent, not affected by addition of NaNO₂, while the b-form develops a red color only after addition of NaNO₂. XVI, treated with CHCl₃ and EtOH-KOH, yields a mixture of 5-methoxyindole-3-aldehyde, m. 178°, and 3-chloro-6-methoxyquinoline, m. 73-4°, separated by steam distillation XVI was also synthesized as follows: 4-Methoxy-2-aldehydophenylglycineamide oxime, yellow, m. 196° (decomposition) was obtained in 70% yield from 5,2-MeO(H₂N)C₆H₃CH:NOH and ClCH₂CONH₂ (formyl derivative, bright yellow, m. 223°); on hydrolysis yields 4-methoxy-2-aldehydophenylglycine oxime, pale yellow, m. 178°; with saturated H₂SO₃ this is changed to 4-methoxy-2-aldehydophenylglycine, bright orange, m. 183° (decomposition) (phenylhydrazone, yellow, m. 175-6°) which yields XVII on boiling with AC₂O and AcONa. V, decomposed at 230-3°, gives 73% of 7-methoxyindole, b₁₇ 157°, b₂₁ 159-61°, slowly turns brown on keeping, fairly volatile with steam (2 g. per 500 cc. H₂O), gives a deep mauve pine-shaving reaction, gives a yellow color with Ehrlich’s reagent, deepening to orange-red on warming and to a deep reddish purple on addition of dilute NaNO₂. Picrate, red, m. 156°. With alc. KOH and CHCl₃ this yields 7-methoxyindole-3-aldehyde, m. 159-60°, and 3-chloro-8-methoxyquinoline, m. 84.5°; the yield of both products was small. VII, at 245-50°, gives 4-methoxyindole, m. 69.5°, (picrate, red, m. 159-60°) gives a deep purple pine-shaving reaction and a reddish purple color with Ehrlich’s reagent. XI decomposes at 210° and gives 75% of 5-methoxyskatole, m. 66°, apparently non-volatile with steam, gives a red pine-shaving reaction and a reddish purple color with Ehrlich’s reagent. Picrate, dark red, m. 151-2°. XII similarly yields 7-methoxyskatole, b₂₀ 170° (picrate, brownish red, m. 156°). The pine-shaving reaction is a deep purplish red; Ehrlich’s reagent gives no color in the cold; on warming a reddish purple color develops. The K derivative of II gives with Me₂SO₄ 2-nitro-α-methoxycinnamic acid (XVIII), pale yellow, m. 164-5°. Na salt, yellow. Me ester, pale yellow, m. 67°; the Et ester appears to be an oil. Oxidation of XVIII gives o-O₂NC₆H₄CHO. Reduction of XVIII with FeSO₄ and NH₄OH gives the 2-amino derivative, pale yellow, crystallines with 2AcOH and m. 167°. Me ester, yellow, m. 60-1°. The acid readily loses MeOH, forming indole-2-carboxylic acid, m. 203-4° (heating above its m. p., solution in cold concentrated H₂SO₄ at room temperature for 16 hrs., boiling with 10% HCl or reduction of XVIII with FeSO₄ and NH₄OH and boiling the reaction product for 24 hrs.). 2-Nitro-α,3-dimethoxycinnamic acid, from IV, as above, m. 202° (decomposition), and reduced to the 2-amino derivative, m. 139°, and decomposing above its m. p. to give V.

Journal of the Chemical Society, Transactions published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate.

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

Londregan, Allyn T. published the artcileSynthesis of Pyridazine-Based α-Helix Mimetics, Recommanded Product: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is ACS Combinatorial Science (2016), 18(10), 651-654, database is CAplus and MEDLINE.

A versatile synthesis of pyridazine-based small mol. α-helix mimetics is presented. Modular C-C, C-N, and C-O bond-forming reactions allow for the inclusion of a variety of aliphatic, basic, aromatic, and heteroaromatic side chain moieties. This robust synthesis is suitable for the preparation of small pyridazine-based libraries.

ACS Combinatorial Science published new progress about 642494-36-8. 642494-36-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Indole,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C14H18BNO2, Recommanded Product: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

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

Zhang, Chufeng published the artcileDiscovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease, Synthetic Route of 166883-20-1, the publication is Journal of Medicinal Chemistry (2021), 64(4), 1966-1988, database is CAplus and MEDLINE.

The design, synthesis, and structure-activity relationships (SARs) of 3-(4-(2-((1H-indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile I [R⁵= 2-cyanoethyl; R⁶ = Me, fluoro; R⁷ = indolin-5-yl, 1-oxoisoindolin-5-yl, 1-tert-butoxycarbonylindol-5-yl, etc.] as selective TYK2 inhibitors was reported. Among them, compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] exhibited acceptable TYK2 inhibition with an IC₅₀ value of 9 nM, showed satisfactory selectivity characteristics over the other three homologous JAK kinases, and performed good functional potency in the JAK/STAT signaling pathway on lymphocyte lines and human whole blood. In liver microsomal assay studied that the clearance rate and half-life of I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] were 11.4 mL/min/g and 121.6 min, resp. Furthermore, in a dextran sulfate sodium colitis model, I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] reduced the production of pro-inflammatory cytokines IL-6 and TNF-α and improved the inflammation symptoms of mucosal infiltration, thickening, and edema. Compound I [R⁵ = 2-cyanoethyl; R⁶ = fluoro; R⁷ = 1-tert-butoxycarbonylindol-5-yl] was aselective TYK2 inhibitor and was used to treat immune diseases and deserved further investigation.

Journal of Medicinal Chemistry published new progress about 166883-20-1. 166883-20-1 belongs to indole-building-block, auxiliary class Indoline,Chloride,Sulfonyl chlorides,Amide, name is 1-Methyl-2-oxoindoline-5-sulfonyl chloride, and the molecular formula is C10H11NO4, Synthetic Route of 166883-20-1.

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

Dolusic, Eduard published the artcileIndol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors, SDS of cas: 20538-12-9, the publication is Bioorganic & Medicinal Chemistry (2011), 19(4), 1550-1561, database is CAplus and MEDLINE.

Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathol. immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biol. activities have been evaluated, leading to compounds with IC₅₀ values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biol. activity, thus corroborating the virtual screening results.

Bioorganic & Medicinal Chemistry published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, SDS of cas: 20538-12-9.

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