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Synlett 2003(2): 0173-0178
DOI: 10.1055/s-2003-36786
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

M. Romero, M. D. Pujol*
Laboratori de Química Farmacèutica (Unitat associada al CSIC), Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, 08028-Barcelona, Spain
e-Mail: mdpujol@farmacia.far.ub.es;
Further Information

Publication History

Received 26 November 2002
Publication Date:
22 January 2003 (online)

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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.

Key words

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

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

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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, Hax-3′ and Hax-5′), 2.47 (dt, J = 11.8, J′ = 4.4, 2 H, Heq-3′ and Heq-5′), 2.70 (dt, J = 11.6, J′ = 2, 2 H, Hax-2′ and Hax-6′), 3.01 (d, J = 11.2, 2 H, Heq-2′ and Heq-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.