Directed ortho-Lithiation of the 2-(N,N-Dimethylhydrazinecarbonyl)-1-methylindole. Efficient Preparation of Tricyclic Lactones

Abstract

N-Methyl indole-2-hydrazide 1 was lithiated at the 3-position using t-BuLi in the presence of TMEDA in THF. The generated ortho-lithiated intermediate is reacted with a variety of electrophiles to give regioselectively 2,3-disubstituted indoles in good yields. The hydroxyhydrazides were converted to the corresponding lactones after oxidation with MnO₂.

indole-hydrazide - directed ortho-metalation (DoM) - 3-oxofuroindole - 2,3-disubstituted indole - hydrazide cleavage

References

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14

The analytical data of 25 are identical to the analytical data of the commercial carboxylic acid purchased from Sigma-Aldrich Co.

15

Analytical data of some representative synthesized compounds: 2-( N , N -Dimethylhydrazinecarbonyl)-1-methylindole ( 1): Mp: 168-170 ºC (hexane-ethyl acetate 2:8). IR (KBr): ν (cm^-1) = 3218 (N-H), 1648 [CONHN(CH₃)₂]. ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 2.71 [s, 6 H, N(CH₃)₂], 4.01 (s, 3 H, NCH₃), 6.81 (br s, 1 H, NH), 7.08-7.39 (m, 3 H, H-4, H-5, H-6), 7.35 (s, 1 H, C3H), 7.61 (d, J = 7, 1 H, H-7). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 31.4 (CH₃, NCH₃), 47.5 [CH₃, N(CH₃)₂], 103.6 (CH, C3H), 109.9 (CH, C7H), 120.3 (CH, C6H), 121.6 (CH, C4H), 123.9 (CH, C5H), 125.8 (C, C3a), 130.5 (C, C2), 138.8 (C, C7a), 160.5 (C, C=O). MS: m/z = 218 [M⁺ + 1]. Anal. Calcd for C₁₂H₁₅N₃O: C, 66.3; H, 7.0; N, 19.3%. Found: C, 66.2; H, 6.9; N, 19.2%. 2-( N , N -Dimethylhydrazinecarbonyl)-1-methyl-3-(4-methoxy-phenylcarbonyl)indole ( 7): Mp: 129-132 ºC (hexane-ethyl acetate 3:7). IR (KBr): ν (cm^-1) = 3196 (N-H), 1674 (ArCOAr), 1610 [CONHN(CH₃)₂]. ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 2.49 [s, 6 H, N(CH₃)₂], 3.53 (s, 3 H, NCH₃), 3.87 (s, 3 H, OCH₃), 6.97 (d, J = 8.8, 2 H, C3′H, and C5′H), 7.01-7.30 (m, 3 H, H-4, H-5, H-6), 7.49 (d, J = 8, 1 H, H-7), 7.80 (d, J = 8.8, 2 H, H-2′ and H-6′), 9.97 (br s, 1 H, NH). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm): 31.2 (CH₃, NCH₃), 46.5 [CH₃, N(CH₃)₂], 55.4 (CH₃, OCH₃), 109.9 (CH, C7H), 113.6 (CH, C3′H and C5′H), 121.3 (C, C2), 121.0, 121.3 and 123.4 (CH, C4H, C5H and C6H), 125.3 (C, C3), 131.8 (CH, C2′H and C6′H), 132.5 (C, C3a), 136.2 (C, C7a and C1′), 159.0 (C, C4′), 163.4 [C, CONHN(CH₃)₂], 190.8 (C, C=O). MS: m/z = 352 [M⁺ + 1]. Anal. Calcd for C₂₀H₂₁N₃O₃: C, 68.4; H, 6.0; N, 12.0%. Found: C, 68.5; H, 5.7; N, 12.1%. 2-( N , N -Dimethylhydrazinecarbonyl)-1-methyl-3-trimethyl-silylindole ( 11): Mp: 148-149 ºC (hexane-ethyl acetate 4:6). IR (KBr): ν (cm^-1) = 3181 (N-H), 1650 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 0.07 [s, 9 H, Si(CH₃)₃], 2.36 [s, 6 H, N(CH₃)₂], 3.35 (s, 3 H, NCH₃), 6.66 (br s, 1 H, NH), 6.70-6.96 (m, 3 H, H-4, H-5, H-6), 7.41 (d, J = 7.8, 1 H, H-7). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 0.73 [CH₃, Si(CH₃)₃], 30.4 (CH₃, NCH₃), 46.9 [CH₃, N(CH₃)₂], 109.6 (CH, C7H), 119.8 (CH, C6H), 121.9 (C, C3), 122.4 and 122.6 (CH, C4H and C5H), 131.8 (C, C2), 137.8 (C, C3a), 139.0 (C, C7a), 162.3 (C, C=O). MS: m/z = 290 [M⁺ + 1]. Anal. Calcd for C₁₅H₂₃N₃OSi: C, 62.2; H, 8.0; N, 14.5%. Found: C, 62.0; H, 7.7; N, 14.4%. 1,3-Dimethyl-2-( N , N -dimethylhydrazinecarbonyl)indole ( 12): Mp: 161-163 ºC (hexane-ethyl acetate 2:8). IR (KBr): ν (cm^-1): 3242 (N-H), 1651 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 2,43 (2, 3 H, C3-CH₃), 2.73 [s, 6 H, N(CH₃)₂], 3.80 (s, 3 H, NCH₃), 6.71-6.79 (br s, 1 H, NH), 7.07-7.39 (m, 3 H, H-4, H-5, H-6), 7.56 (d, J = 8, 1 H, H-7). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 10.1 (CH₃, C3-CH₃), 31.0 (CH₃, NCH₃), 47.7 [CH₃, N(CH₃)₂], 109.6 (CH, C7H),), 111.8 (C, C3), 119.4 (CH, C6H), 119.8 (CH, C4H), 123.8 (CH, C5H), 127.0 (C, C3a), 128.9 (C, C2), 137.7 (C, C7a), 160.8 (C, C=O). MS: m/z = 232 [M⁺ + 1]. Anal. Calcd for C₁₃H₁₇N₃O: C, 67.5; H, 7.4; N, 18.2%. Found: C, 67.4; H, 7.6; N, 18.3%. 3-Ethyl-2-( N , N -dimethylhydrazine-carbonyl)-1-methylindole ( 13): Mp: 146-149 ºC (hexane-ethyl acetate 2:8). IR (KBr): ν (cm^-1) = 3202 (N-H), 1651 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 1.32 (t, J = 7.6, 3 H, CH₂CH ₃ ), 2.76 [s, 6 H, N(CH₃)₂], 2.93 (q, J = 7.6, 2 H, CH ₂ CH₃), 3.85 (s, 3 H, NCH₃), 6.58-6.60 (br s, 1 H, NH), 7.05-7.37 (m, 3 H, H-4, H-5, H-6), 7.63 (d, J = 8.2, 1 H, H-7). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 16.1 (CH₃, CH₂CH ₃ ), 18.3 (CH₂, CH ₂ CH₃), 31.0 (CH₃, NCH₃), 47.6 [CH₃, N(CH₃)₂], 109.7 (CH, C7H), 111.8 (C, C3), 119.4 (CH, C6H), 119.9 (CH, C4H), 123.7 (CH, C5H), 126.1 (C, C3a), 128.5 (C, C2), 137.7 (C, C7a), 160.9 (C, C=O). MS: m/z = 246 [M⁺ + 1]. Anal. Calcd for C₁₄H₁₉N₃O: C, 68.5; H, 7.8; N, 17.1. Found: C, 68.4; H, 7.6; N, 17.3.
3-(2-Carboxyethyl-1-carbonyl)-2-( N , N -dimethylhydra-zinecarbonyl)-1-methylindole ( 14): Mp: 120-123 ºC (ethyl acetate-methanol 9:1). IR (KBr): ν (cm^-1): 3483 (O-H), 3201 (N-H), 1725 (C=O), 1649 (C=O, CONHNMe₂). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 2.74 (t, J = 5.6, 2 H, CH₂CO₂H), 2.83 [s, 6 H, N(CH₃)₂], 3.20 (t, J = 5.6, 2 H, CH₂CO), 3.66 (s, 3 H, NCH₃), 7.05-7.39 (m, 4 H, H-4, H-5, H-6, CO₂H), 7.89 (d, J = 8, 1 H, H-7), 8.43 (br s, 1 H, NH). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 28.5 (CH₂, CH₂CO), 31.4 (CH₃, NCH₃), 36.5 (CH₂, CH₂CO₂H), 46.7 [CH₃, N(CH₃)₂], 110.5 (CH, C7H), 115.0 (C, C3), 121.3 (CH, C6H), 121.4 (CH, C4H), 124.1 (CH, C5H), 121.3 (C, C2), 124.3 (C, C3a), 136.6 (C, C7a), 160.6 (C, CONHNMe₂), 177.1 (C, CO₂H), 195.5 (C, C=O). MS: m/z = 318 [M⁺ + 1]. Anal. Calcd for C₁₆H₁₉N₃O₄: C, 60.6; H, 6.0; N, 13.2. Found: C, 60.3; H, 6.2; N, 13.2. 3-(Allyloxycarbonyl)-2-( N , N -dimethylhydrazine-carbonyl)indole ( 15): Hexane-ethyl acetate 2:8. IR (NaCl): ν (cm^-1) = 3200 (N-H), 1693 (COOR), 1670 [CONHN(CH₃)₂]. ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 2.77 [s, 6 H, N(CH₃)₂], 4.01 (s, 3 H, NCH₃), 4.89 (d, J = 6, 2 H, CH₂O), 5.37 (m, 2 H, CH ₂ =CH), 6.10 (m, 1 H, CH₂=CH), 6.80 (br s, 1 H, NH), 7.32 (m, 3 H, H-4, H-5, H-6), 8.15 (d, J = 7, 1 H, H-7). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 32.4 (CH₃, NCH₃), 47.3 [CH₃, N(CH₃)₂], 65.5 (CH₂, CH₂O), 113.3 (CH, C7H), 118.6 (CH₂, CH ₂ =CH), 121.2 (C, C3), 122.8 (CH, C6H), 122.9 (CH, C4H), 124.4 (CH, C5H), 125.3 (C, C2), 132.1 (CH, CH₂=CH), 136.8 (C, C7a), 137.2 (C, C3a), 159.6 (C, COO-), 165.8 (C, CON-). MS: m/z = 302 [M⁺ + 1]. Anal. Calcd for C₁₆H₁₉N₃O₃: C, 63.8; H, 6.4; N, 13.9. Found: C, 63.5; H, 6.7; N, 13.8. 3-( t -Butylcarbonyl)-2-( N , N -dimethylhydrazinecarbonyl)-1-methylindole ( 16): Mp: 149-150 ºC (hexane-ethyl acetate 3:7). IR (KBr): ν (cm^-1) = 3226 (N-H), 1662 (C=O, CONHNMe₂). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 1.28 [s, 9 H, C(CH₃)₃], 2.67 [s, 6 H, N(CH₃)₂], 3.93 (s, 3 H, NCH₃), 7.05-7.38 (m, 3 H, H-4, H-5, H-6), 7.51 (d, J = 8, 1 H, H-7), 7.52 (br s, 1 H, NH). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 27.1 [CH₃, C(CH₃)₃], 31.3 (CH₃, NCH₃), 45.9 [C, C(CH₃)₃], 47.5 [CH₃, N(CH₃)₂], 110.2 (CH, C7H), 116.8 (C, C3), 121.0 (CH, C6H), 121.4 (CH, C4H), 124.1 (CH, C5H), 124.2 (C, C3a), 129.6 (C, C2), 136.7 (C, C7a), 159.7 (C, CONHNMe₂), 213.7 (C, C=O). MS: m/z = 302 [M⁺ + 1]. Anal. Calcd for C₁₇H₂₃N₃O₂: C, 67.7; H, 7.7; N, 13.9. Found: C, 67.5; H, 7.9; N, 13.6. 1,4-Dimethyl-3-oxo-(1 H )-furo[3,4- b ]indole ( 17): Mp: 84-85 ºC (hexane-ethyl acetate 8:2). IR (KBr): ν (cm^-1) = 2932 (C-H), 1751 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 1.70 (d, J = 6.6, 3 H, CHCH ₃ ), 3.91 (s, 3 H, NCH₃), 5.64 (q, J = 6.6, 1 H, CHCH₃), 7.20-7.27 (m, 1 H, H-7), 7.41-7.60 (m, 2 H, H-6, H-8), 7.61 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 20.7 (CH₃, CHCH ₃ ), 30.0 (CH₃, NCH₃), 75.4 (CH, CHCH₃), 111.2 (CH, C5H), 119.8 (C, C8b), 120.6 and 120.8 (CH, C6H and C8H), 125.9 (CH, C7H), 128.5 (C, C3a), 138.2 (C, C8a), 143.9 (C, C4a), 163.2 (C, C=O). MS: m/z = 202 [M⁺ + 1]. Anal. Calcd for C₁₂H₁₁NO₂: C, 71.6; H, 5.5; N, 7.0. Found: C, 71.5; H, 5.7; N, 6.8. 1-Hexyl-4-methyl-3-oxo-(1 H )-furo[3,4- b ]indole ( 18): Hexane-ethyl acetate 9:1. IR (NaCl): ν (cm^-1) = 2928 (C-H), 1752 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 0.91 [d, J = 6, 3 H, (CH₂)₅CH₃], 1.21-1.63 [m, 8 H, CH₂(CH ₂ )₄CH₃], 1.82-2.10 [m, 2 H, CH ₂ (CH₂)₄CH₃], 3.94 (s, 3 H, NCH₃), 5.58 (q, J = 6, 1 H, C1H), 7.23-7.46 (m, 3 H, H-6, H-7, H-8), 7.62 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 14.0 [CH₃, (CH₂)₅CH ₃ ], 22.5 [CH₂, (CH ₂ )₅CH₃], 24.8 [CH₂, (CH ₂ )₅CH₃], 29.0 [CH₂, (CH ₂ )₅CH₃], 30.0 (CH₃, NCH₃), 31.6 [CH₂, (CH ₂ )₅CH₃], 34.6 [CH₂, (CH ₂ )₅CH₃], 79.4 (CH, C1H), 111.2 (CH, C5H), 120.1 (C, C8b), 120.8 and 121.0 (CH, C6H and C8H), 125.8 (CH, C7H), 128.8 (C, C3a), 137.0 (C, C8a), 144.0 (C, C4a), 163.4 (C, C=O). MS: m/z = 272 [M⁺ + 1]. Anal. Calcd for C₁₇H₂₁NO₂: C, 75.2; H, 7.8; N, 5.2. Found: C, 75.1; H, 7.7; N, 4.9. 1-t -Butyl-4-methyl-3-oxo-(1 H )-furo[3,4- b ]indole ( 19): Mp: 171-173 ºC (hexane-ethyl acetate 9:1). IR (KBr): ν (cm^-1) = 2963 (C-H), 1749 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 1.11 [s, 9 H, C(CH₃)₃], 3.97 (s, 3 H, NCH₃), 5.26 (s, 1 H, H-1), 7.21-7.28 (m, 1 H, H-7), 7.39-7.45 (m, 2 H, H-6, H-8), 7.68 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 25.5 [CH₃, C(CH₃)₃], 30.0 (CH₃, NCH₃), 35.4 [C, C(CH₃)₃], 87.6 (CH, C1H), 111.2 (CH, C5H), 120.8 (C, C8b), 120.9 and 122.2 (CH, C6H and C8H), 125.9 (CH, C6H), 129.9 (C, C3a), 134.7 (C, C8a), 144.0 (C, C4a), 163.6 (C, C=O). MS: m/z = 244 [M⁺ + 1]. Anal. Calcd for C₁₅H₁₇NO₂: C, 74.0; H, 7.0; N, 5.8. Found: C, 74.3; H, 6.9; N, 5.8. 1-Benzyl-oxymethyl-4-methyl-3-oxo-(1 H )-furo[3,4- b ]indole ( 20): Mp: 116-118 ºC (hexane-ethyl acetate 9:1). IR (KBr): ν (cm^-1) = 2932 (C-H), 1748 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 3.90 (d, J = 6, 2 H, CH₂O), 3.91 (s, 3 H, NCH₃), 4.65 (s, 2 H, CH₂O), 5.70 (q, J = 6, 1 H, C1H), 7.24 (m, 1 H, Ar), 7.42 (m, 5 H, Ar), 7.46 (m, 2 H, Ar), 7.64 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 30.0 (CH₃, NCH₃), 71.4 (CH₂, CH₂O), 73.8 (CH₂, CH₂O), 77.8 (CH, C1H), 111.1 (CH, C5H), 120.4 (C, C8b), 121.0 and 121.6 (CH, C6H and C8H), 126.0 (CH, C4′H), 127.6 (CH, C7H), 127.7 (CH, C2′H and C6′H), 128.3 (CH, C3′H and C5′H), 128.9 (C, C3a), 134.7 (C, C8a), 137.3 (C, C1′), 144.0 (C, C4a), 162.9 (C, C=O). MS: m/z = 308 [M⁺ + 1]. Anal. Calcd for C₁₉H₁₇NO₃: C, 74.3; H, 5.6; N, 4.6. Found: C, 74.0; H, 5.7; N, 4.4. 1-(3′-(Trifluoromethane)phenyl)-4-methyl-3-oxo-(1 H )-furo[3,4- b ]indole ( 21): Hexane-ethyl acetate 8:2. IR (NaCl): ν (cm^-1) = 2919 (C-H), 1759 (C=O), 1331 (C-F). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 4.02 (s, 3 H, NCH₃), 6.59 (s, 1 H, H-1), 7.19-7.60 (m, 6 H, H-4′, H-5′, H-6′, H-6, H-7, H-8), 7.64 (d, J = 7, 1 H, H-5), 7.71 (s, 1 H, H-2′). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 30.0 (CH₃, NCH₃), 79.2 (CH, C1H), 111.5 (CH, C5H), 120.2 (C, C8b), 120.8 and 121.5 (CH, C6H and C8H), 125.6 (C, J = 288, CF₃), 125.9 (CH, J = 3.6, C4′H), 126.4 (CH, C7H), 128.5 (CH, J = 3.6, C2′H), 128.9 (C, C3a), 129.4 (CH, C5′H), 130.3 (CH, C6′H), 130.6 (C, J = 32, C3′), 131.9 (C, J = 1, C1′), 141.0 (C, C8a), 144.4 (C, C4a), 162.7 (C, C=O). MS: m/z = 332 [M⁺ + 1]. Anal. Calcd for C₁₈H₁₂F₃NO₂: C, 65.3; H, 3.7; N, 4.2. Found: C, 65.5; H, 3.9; N, 4.4. 4′-Methyl-3-oxo-(1 H )spiro{cyclo-hexyl[1,1′]furo[3,4- b ]indole} (22): Mp: 152-154 ºC (hexane-ethyl acetate 9:1). IR (KBr): ν (cm^-1): 2921 (C-H), 1749 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 1.50-2.08 (m, 10 H, CH₂), 3.93 (s, 3 H, NCH₃), 7.18-7.27 (m, 1 H, H-7), 7.39-7.44 (m, 2 H, H-6, H-8), 7.68 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz):
δ (ppm) = 22.5 (CH₂, C3′H and C5′H), 24.6 (CH₂, C4′H), 30.0 (CH₃, NCH₃), 36.7 (CH₂, C2′H and C6′H), 86.0 (C, C1), 111.2 (CH, C5H), 119.8 (C, C8b), 120.7 and 121.1 (CH, C6H and C8H), 125.7 (CH, C7H), 128.2 (C, C3a), 138.2 (C, C8a), 143.9 (C, C4a), 163.2 (C, C=O). MS: m/z = 256 [M⁺ + 1]. Anal. Calcd for C₁₆H₁₇NO₂: C, 75.3; H, 6.7; N, 5.5. Found: C, 75.2%, H, 6.9; N, 5.2. 1′-Benzyl-4-methyl-3-oxo-(1 H )-spiro{furo[3,4- b ]indole-1,4¢-piperidine} (23): Hexane-ethyl acetate 8:2. IR (NaCl): ν (cm^-1) = 1755 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 1.87 (d, J = 12.8, 2 H, H_ax-3′ and H_ax-5′), 2.47 (dt, J = 11.8, J′ = 4.4, 2 H, H_eq-3′ and H_eq-5′), 2.70 (dt, J = 11.6, J′ = 2, 2 H, H_ax-2′ and H_ax-6′), 3.01 (d, J = 11.2, 2 H, H_eq-2′ and H_eq-6′), 3.74 (s, 2 H, CH₂Ar), 3.92 (s, 3 H, NCH₃), 7.11-7.42 (m, 8 H, H-6, H-7, H-8, H-2′′, H-3′′, H-4′′, H-5′′ and H-6′′), 7.63 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 30.1 (CH₃, NCH₃), 35.7 (CH₂, C3′ and C5′), 49.2 (CH₂, C2′ and C6′), 62.5 (CH₂, CH₂Ar), 82.9 (C, C1), 111.2 (CH, C5H), 119.6 (C, C8b), 120.8 and 121.0 (CH, C6H and C8H), 126.0 (CH, C7H), 127.5 (CH, C4′′H), 128.1 (C, C3a), 128.3 (CH, C2′′H and C6′′H), 129.6 (CH, C3′′H and C5′′H), 136.4 (C, C1′′), 140.4 (C, C8a), 143.9 (C, C4a), 162.5 (C, C=O). MS: m/z = 347 [M⁺ + 1]. Anal. Calcd for C₂₂H₂₂N₂O₂: C, 76.3; H, 6.4; N, 8.1. Found: C, 76.1; H, 6.6; N, 8.3. 1-(Cynnamyl)-2-( N , N -dimethylamino)-4-methyl-3-oxo-(1 H )-pirrolo[3,4- b ]indole ( 24): Mp: 170-172 ºC (hexane-ethyl acetate 7:3). IR (KBr): ν (cm^-1): 2925 (C-H), 1682 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm): 3.01 [s, 6 H, N(CH₃)₂], 4.00 (s, 3 H, NCH₃), 5.19 (d, J = 8.4, 1 H, H-1), 6.13 (dd, J = 15.7, J′ = 8.2, 1 H, CHCHAr), 6.79 (d, J = 15.6, 1 H, CHCHAr), 7.10-7.45 (m, 8 H, H-2′, H-3′, H-4′, H-5′, H-6′, H-6, H-7, H-8), 7.56 (d, J = 8, 1 H, H-5). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 30.2 (CH₃, NCH₃), 45.0 [CH₃, N(CH₃)₂], 60.6 (CH, C1H), 110.1 (CH, C8H), 120.0 (CH, C5H), 120.5 (CH, C6H), 121.7 (C, C8b), 124.2 (CH, C7H), 124.6 (C, C8a), 126.3 (CH, CHCHAr), 126.6 (CH, C3′H and C5′H), 128.0 (CH, C4′H), 128.6 (CH, C2′H and C6′H), 132.5 (C, C3a), 133.9 (CH, CHCHAr), 136.3 (C, C1′), 141.9 (C, C4a), 162.5 (C, C=O). MS: m/z = 332 [M⁺ + 1]. Anal. Calcd for C₂₁H₂₁N₃O: C, 76.1; H, 6.4; N, 12.7. Found: C, 76.2; H, 6.7; N, 12.5. 1-Methyl-3-(4-methoxyphenylcarbonyl)indole-2-yl-carboxylic acid ( 26): Mp: 124-126 ºC (hexane-ethyl acetate, 7:3). IR (KBr): ν (cm^-1): 2959 (O-H), 1715 (C=O). ¹H NMR (CDCl₃, 200 MHz): δ (ppm) = 3.93 (s, 3 H, NCH₃), 4.25 (s, 3 H, OCH₃), 6.98 (d, J = 8.8, 2 H, C3′H, and C5′H), 7.03-7.45 (m, 4 H, H-4, H-5, H-6, CO₂H), 7.54 (d, J = 8.4, 1 H, H-7), 7.84 (d, J = 8.8, 2 H, H-2′ and H-6′). ¹³C NMR (CDCl₃, 50.3 MHz): δ (ppm) = 33.0 (CH₃, NCH₃), 55.6 (CH₃, OCH₃), 111.0 (CH, C7H), 113.7 (CH, C3′H and C5′H), 116.8 (C, C2), 122.6, 122.8 and 125.6 (CH, C4H, C5H and C6H), 125.8 (C, C3), 131.0 (C, C1′), 132.7 (CH, C2′H and C6′H), 133.2 (C, C3a), 137.5 (C, C7a), 161.4 (C, C4′), 164.1 (C, CO₂H), 194.6 (C, C=O). MS: m/z = 310 [M⁺ + 1]. Anal. Calcd for C₁₈H₁₅NO₄: C, 69.9; H, 4.9; N, 4.5. Found: C, 69.7; H, 5.2; N, 4.2.