Category: 20538-12-9

Ren, Long published the artcileCarboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling, Related Products of indole-building-block, the publication is Journal of Organic Chemistry (2018), 83(23), 14472-14488, database is CAplus and MEDLINE.

The cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured by the broad substrate scope and the use of ambient oxygen as an oxidant and is convenient and economical for both laboratory and industry applications. The existence of the labile hydrogen at C-3 and the highly transformable carbonyl at C-2 makes the indoles versatile building blocks for organic synthesis in different contexts. Computational studies based on the d. functional theory (DFT) suggest that the rate-determining step is carboxylic acid-assisted condensation of the substrates, rather than the functionalization of aryl C-H. Accordingly, a pathway via imine intermediates is deemed to be the preferred mechanism. In contrast to the general deduction, the in situ formed imine, instead of its enamine isomer, is believed to be involved in the first ligand exchange and later carbopalladation of the α-Me, which shed new light on this indolization mechanism.

Journal of Organic 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, Related Products of 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

Ishii, Hisashi published the artcileFischer indolization and its related compounds. V. Indolization of ethyl pyruvate 2-methoxyphenylhydrazone and its N-methyl derivative with protic acids. Unpredictable products and the mechanism, Formula: C12H13NO3, the publication is Chemical & Pharmaceutical Bulletin (1973), 21(7), 1481-94, database is CAplus.

Fischer indolization of Et pyruvate 2-methoxyphenylhydrazone (I) and its N-Me derivative with protic acids gives mainly 6-substituted indole derivatives formed by substitution of the MeO group of I with nucleophiles in the reaction medium. The mechanism involved the cation II as the key intermediate in the formation of the unexpected indole products.

Chemical & Pharmaceutical Bulletin 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, Formula: C12H13NO3.

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

Ishii, Hisashi published the artcileFischer indolization and its related compounds. VI. Effect of reagents and substituent of the o-substituted phenylhydrazone on abnormal Fischer indolization, COA of Formula: C12H13NO3, the publication is Chemical & Pharmaceutical Bulletin (1973), 21(7), 1495-505, database is CAplus.

Treatment of Et pyruvate 2-methoxyphenylhydrazone (I) with Lewis acid gave 5-substituted and/or 5-methoxyindoles with Et 7-methoxy-indole-2-carboxylate as the main product in contrast with the abnormal Fischer indolization of I. Differences of the acid strength of the reagent and of the electron d. on a benzene ring due to introduction of some other addnl. substituents was the determinant for the abnormal transformation.

Chemical & Pharmaceutical Bulletin 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, COA of Formula: C12H13NO3.

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

Ishii, Hisashi published the artcileSubstitution and migration of methoxyl group in the Fischer indolization of ethyl pyruvate 2-methoxyphenylhydrazone, Computed Properties of 20538-12-9, the publication is Tetrahedron Letters (1970), 1181-4, database is CAplus.

The indolization of 2-MeOC6H4NHN:CMeCO2Et (I) with 3M HCl-EtOH gave Et 6-chloroindole-2-carboxylate, Et 7-methoxyindole-2-carboxylate (II), and Et 6-ethoxyindole-2-carboxylate. The treatment of I with BF3 in AcOH or AcOEt gave IIk, Et indole-2-carboxylate (III), and Et 5-methoxyindole-2-carboxylate (IV). The treatment of I with H2SO4, in AcOH gave II, III, and IV. A mechanism involving substitution and migration of the MeO group is discussed.

Tetrahedron Letters 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, Computed Properties of 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

Ishii, Hisashi published the artcileFischer indolization and its related compounds. XIII. Measurement of the nuclear magnetic resonance spectra of ethyl indole-2-carboxylate derivatives using the shift reagent and its application, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Yakugaku Zasshi (1979), 99(4), 413-20, database is CAplus and MEDLINE.

Proton NMR spectra of several Et indole-2-carboxylate derivatives in the presence of a shift reagent, tris(dipivalomethanato)-europium [Eu(DPM)₃], were measured in CDCl₃ and good straight lines were obtained on plotting induced shift vs. concentration of Eu(DPM)₃ for each signal. Application of the McConnell-Robertson equation to interpret pseudocontact shifts of the indole derivatives gave good agreement between measured and predicted shifts. The relation between substituents of indoles and the position of the coordinated Eu atom is discussed.

Yakugaku Zasshi 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

Ishii, Hisashi published the artcileFischer indolization and its related compounds. VIII. Formation of 4-aminoindole derivatives on the Fischer indolization of 2-methoxyphenylhydrazone derivatives, Recommanded Product: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Chemical & Pharmaceutical Bulletin (1974), 22(9), 1981-9, database is CAplus.

Fischer indolization of Et pyruvate 5-chloro-2-methoxyphenylhydrazone with ZnCl2 gave Et 4-amino-6-chloroindole-2-carboxylate (I,R = 4-NH2R1 = 6-Cl) together with I (R = 5-Cl, 5-OMe, R1 = 6-Cl; R = 4-Cl, R1 =7-OMe). Cyclization of Et Pyruvate 2-methoxyphenylhydraxone with p-toluenesulfonic acid in the presence of malonate gave Et 4-(ethoxycarbonylacetamido)indole-2-carboxylate and di-Et 4-(ethoxycarbonylacetamido)-3,6′-biindole-2,2-dicarboxylate with I (R = H, R1 = 5-OMe, 7-OMe,5-O3SC6H4Me-p) and aminoindole product in the abnormal Fisher indolization of a 2-methoxyphenylhydrazone derivative is discussed.

Chemical & Pharmaceutical Bulletin 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, Recommanded Product: 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

Ishii, Hisashi published the artcileAbnormal Fischer indolization and its related compounds. XII. Synthesis of 3,6′-biindole, Application In Synthesis of 20538-12-9, the publication is Chemical & Pharmaceutical Bulletin (1979), 27(2), 346-50, database is CAplus.

Fisher indole reaction of Et indole-2-carboxylate with (E)-2-MeOC₆H₄NHN:CMeCO₂Et (I) in refluxing C₆H₆ containing MeC₆H₄SO₃H gave 12.2% Et 7-methoxyindole-2-carboxylate and 28.4% biindole II (R = CO₂Et). Saponification of II (R = CO₂Et) gave II (R = CO₂H) which was decarboxylated by heating in quinoline containing Cu-chromite to give 3,6′-diindole (II; R = H). Treatment of indole with I in refluxing C₆H₆ containing MeC₆H₄SO₃H gave 11.3% Z–I, 25.6% diindolylpropionate III, and 17.3% indole trimer IV.

Chemical & Pharmaceutical Bulletin 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, Application In Synthesis of 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

Ishii, H. published the artcileFischer indolization and its related compounds. VII. Development of abnormal Fischer indolization of o-methoxyphenylhydrazone to provide a synthetic method for useful indole derivatives possessing an active methine group at C-6 and novel 3,6′-biindole derivatives, SDS of cas: 20538-12-9, the publication is Tetrahedron (1973), 29(14), 1991-2003, database is CAplus.

o-MeOC6H4NHN:CMeCO2Et (I) with p-MeC6H4SO3H in C6H6 in the presence of MeCOCH2COR (R = Me and OEt) gave Et 6-(1-acetyl-2-oxopropyl)indole-2-carboxylate (II, R = Me) and Et α-acetyl-2-(ethoxycarbonyl)indole-6-acetate (II, R = OEt), resp. Under similar conditions, I with Et 6-chloroindole-2-carboxylate gave di-Et 6-chloro-3,6′-biindole-2,2′-dicarboxylate (III, R = Cl, R1 = OH) and Et 5-(p-tolylsulfonyloxy)indole-2-carboxylate. Similarly, I with Et 7-methoxyindole-2-carboxylate gave di-Et 7-methoxy-4,6′-biindole-2,2′-dicarboxylate and III (R = H, R1 = OMe).

Tetrahedron 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

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

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