Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[N:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH:19]([CH2:29]OS(C)(=O)=O)[C:12]2=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[Cl-:36]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[N:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH:19]([CH2:29][Cl:36])[C:12]2=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CC(COS(C)(=O)=O)c2c1cc(OCc1ccccc1)c1ncccc21
Reactant: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC(CCl)c2c1cc(OCc1ccccc1)c1ncccc21
Temperature: 0 °C
Yield: 91.8 %

Procedure:
A solution of 8-methoxy-6-nitroquinoline (2) [prepared from 2-methoxy-4-nitroaniline 1 by the method of Battersby et al., J. Chem., Soc. Perkin Trans. 1, 1979, 2550] (50.0 g, 0.245 mol) in 48% aqueous HBr (0.205 L, 1.22 mol) was stirred at reflux for 65 h. The mixture was cooled in ice and the precipitate was removed by filtration and dried in a desiccator to give 3 as the hydrobromide salt (58.0 g, 87%): subl. 140° C., mp>230° C; 1H NMR (DMSO) δ 10.69 (br s, 2 H), 9.20 (dd, J=4.9, 1.5 Hz, 1 H), 9.11 (dd, J=8.5, 1.5 Hz, 1 H), 8.64(d, J=2.4 Hz, 1 H), 8.05 (dd, J=8.5, 4.9 Hz, 1 H), 7.90 (d, J=2.4 Hz, 1 H); 13C NMR (DMSO) δ 152.0, 149.4, 146.4, 144.3, 135.4, 128.3, 124.1, 114.5, 106.5. Anal. Calcd for C9H6N2O3.HBr: C, 40.01; H, 2.61; N, 10.37. Found: C, 40.44; H, 2.17; N, 10.83. 8-Benzyloxy-6-nitroquinoline (4). A mixture of 3 (58.0 g, 0.214 mol), DMF (400 mL), K2CO3 (103.5 g, 0.75 mmol), and NaI (1.60 g, 10.7 mmol) was stirred at room temperature, while benzyl bromide (25.4 mL, 0.214 mmol) was added in four portions at half hourly intervals. A total of 9 h after the first addition, the mixture was poured onto ice (1.5 kg) and the precipitate was removed by filtration, washed with water, and dried. The crude material was dissolved in CH2Cl2 and the solution was filtered through alumina to give 4 (59.55 g, 99%): mp (EtOH) 152–153° C.; 1H NMR (CDCl3) δ 9.13 (dd, J=4.2, 1.8 Hz, 1 H), 8.35 (d, J=2.3 Hz, 1 H), 8.29 (dd, J=8.4, 1.8 Hz, 1 H), 7.83 (d, J=2.3 Hz, 1 H), 7.59 (dd, J=8.4, 4.2 Hz, 1 H), 7.56 (d, J=7.6 Hz, 2 H), 7.40 (dd, J=7.6, 7.2 Hz, 2 H), 7.33 (t, J=7.2 Hz, 1 H), 5.50 (s, 2 H); 13C NMR (CDCl3) δ 155.4, 152.5, 145.6, 142.6, 137.9, 135.4, 128.8, 128.4, 127.8, 127.5, 123.3, 116.3, 103.1, 71.4. Anal. Calcd. for C16H12N2O3: C, 68.57; H, 4.32; N, 9.99. Found: C, 68.51; H, 4.29; N, 10.04. 6-Amino-8-benzyloxyquinoline (5). Iron dust (16.0 g, 0.285 mol) was added to a solution of 4 (8.00 g, 28.5 mmol) and AcOH (16 mL, 0.285 mol) in EtOH-water (5:1, 240 mL) at reflux. After 10 min, the mixture was carefully poured into saturated aqueous NaHCO3 (300 mL). The mixture was filtered through Celite and the filter cake was washed with water (100 mL), EtOH (3×50 mL), and CH2Cl2 (3×100 mL). The combined filtrates were diluted with water (300 mL) and the aqueous layer was separated and extracted with CH2Cl2 (2×50 mL). The combined extracts were washed with water, dried (Na2SO4), and evaporated to give 5 (7.13 g, 100%) as a tan solid: mp 183–185° C.; 1H NMR (CDCl3) δ 8.66 (dd, J=4.2, 1.6 Hz, 1 H), 7.84 (dd, J=8.3, 1.6 Hz, 1 H), 7.48 (dd, J=8.1, 1.7 Hz, 2 H), 7.23–7.39 (m, 3 H), 7.28 (dd, J=8.3, 4.2 Hz, 1 H), 6.51, 6.48 (2×d, J=2.3 Hz, 1 H each), 5.36 (s, 2 H), 3.85 (br s, 2 H); 13C NMR (CDCl3) δ 155.2, 155.7, 144.8, 136.8, 135.9, 133.5, 130.8, 128.6, 127.8, 127.0, 122.0, 102.6, 100.0, 70.6. Anal. Calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19. Found C, 76.54; H, 5.61; N, 11.15. 8-Benzyloxy-6-(tert-butyloxycarbonylamino)quinoline (6). A mixture of 5 (7.63 g, 30.5 mmol), BOC2O (8.65 g, 39.6 mmol) and dioxane (70 mL) was stirred at reflux for 2 h. Further BOC2O (0.86 g, 4.0 mmol) was added and the mixture was heated at reflux for another 1 h. The dioxane was evaporated, the remaining oil was triturated with pentane, and the resulting solid was removed by filtration, dissolved in CH2Cl2 and filtered through alumina to give 6 (10.42 g, 98%) as a cream solid: mp 180–181° C.; 1H NMR (CDCl3) δ 8.77 (dd, J=4.2, 1.6 Hz, 1 H), 7.98 (dd, J=8.3, 1.6 Hz, 1 H), 7.55 (d, J=2.1 Hz, 1 H), 7.41 (dd, J=7.4, 2.2 Hz, 2 H), 7.34 (dd, J=8.3, 4.2 Hz, 1 H), 7.20–7.29 (m, 3 H), 7.02 (d, J=2.1 Hz, 1 H), 5.28 (s, 2 H), 1.49 (s, 9 H); 13C NMR (CDCl3) δ 154.6, 152.7, 147.4, 137.2, 136.8, 136.3, 135.2, 129.9, 128.4, 127.7, 127.2, 122.0, 105.8, 103.5, 80.6, 70.6, 28.2. Anal. Calcd for C21H22N2O3: C, 71.98; H, 6.33; N, 7.99. Found C, 71.80; H, 6.31; N, 7.98. 8-Benzyloxy-6-(tert-butyloxycarbonylamino)-5-iodoquinoline (7a). A mixture of 6 (1.04 g, 3.0 mmol), NIS (0.70 g, 3.1 mmol) and CH3CN (10 mL) was stirred at reflux for 30 min. Further NIS (40 mg, 0.18 mmol) was added and the mixture stirred at reflux for a further 30 min. The CH3CN was evaporated and the residue was taken up in EtOAc (30 mL) and washed with a solution of Na2S2O5 and Na2CO3 in water (×3). The aqueous washes were back extracted with EtOAc (×2). The combined organic extracts were washed with water, dried (brine, MgSO4), filtered through silica gel, and evaporated to give 7a (1.33 g, 93%), which crystallized from hexane as tan needles: mp 118–119° C.; 1H NMR (CDCl3) δ 8.79 (dd, J=4.2, 1.4 Hz, 1 H), 8.32 (dd, J=8.6, 1.4 Hz, 1 H), 8.29 (s, 1 H), 7.59 (dd, J=8.0, 1.7 Hz, 2 H), 7.43 (dd, J=8.6, 4.2 Hz, 1 H), 7.25–7.39 (m, 3 H), 7.24 (br s, 1 H), 5.43 (s, 2 H), 1.57 (s, 9 H); 13C NMR (CDCl3) δ 155.2, 152.4, 148.1, 139.5, 138.9, 138.3, 136.2, 130.7, 128.5, 128.0, 123.4, 103.9, 81.5, 78.1, 71.0, 28.3. Anal. Calcd for C21H21IN2O3: C, 52.96; H, 4.44; N, 5.88. Found C, 53.18; H, 4.39; N, 5.95. 8-Benzyloxy-6-[N-(tert-butyloxycarbonyl)-N-(3,3-dimethoxypropyl)amino]-5-iodoquinoline (8a). NaH (60% in oil, 92 mg, 2.3 mmol) under nitrogen was washed with pentane (2×2 mL), cooled (ice-water) and treated with a solution of 7a (1.00 g, 2.10 mmol) in DMF (10 mL) over 5 min. The mixture was allowed to warm to room temperature and stir for 30 min, over which time it became bright yellow and effervescence ceased A solution of 3-bromo-1,1-dimethoxypropane (0.69 g, 3.77 mmol) in DMF (0.5 mL) was added and the mixture was stirred at room temperature for 22 h. The mixture was poured into pH 7.4 phosphate buffer (50 mL) and extracted with EtOAc (3×20 mL). The combined extracts were washed with water (2×50 mL), dried (brine, Na2SO4), evaporated, and purified by dry-flash column chromatography (silica gel, 10–90% EtOAc/hexane), to give 8a (1.00 g, 83%) as a cream powder: mp 120–121° C.; 1H NMR (CDCl3) major rotamer δ 8.94 (br d, J=2.9 Hz, 1 H), 8.52 (dd, J=8.6, 1.5 Hz, 1 H), 7.45–7.58 (m, 3 H), 7.25–7.40 (m, 3 H), 6.96 (br s, 1 H), 5.46 (s, 2 H), 4.40 (t, J=4.7 Hz, 1 H), 3.84 (br ddd, J=14.6, 7.3, 7.3 Hz, 1 H), 3.33 (ddd, J=14.6, 8.2, 5.8 Hz, 1 H), 3.28, 3.25 (2×s, 3 H each), 1.65–1.95 (m, 2 H), 1.23 (br s, 9 H); 13C NMR (CDCl3) major rotamer δ 154.6, 153.6, 149.9, 143.8, 141.3, 139.8, 136.0, 131.2, 128.7, 128.0, 127.0, 123.4, 112.3, 102.9, 93.3, 80.3, 70.9, 53.1, 52.7, 45.4, 31.2, 28.1; C26H31IN2O5 requires M+. 578.1278. Found 578.1257. 8-Benzyloxy-6-[N-(tert-butyloxycarbonyl)-N-(3-oxopropyl)amino]-5-iodoquinoline (9a). A solution of 8a (0.75 g, 1.30 mmol), TsOH.H2O (0.12 g, 0.65 mmol) and water (3.75 mL) in acetone (38 mL) was stirred at reflux for 2.25 h. Most of the acetone was evaporated and the residue was diluted with water (50 mL) and saturated aqueous NaHCO3 (5 mL) and extracted with EtOAc (3×20 mL). The combined extracts were washed with water (2×50 mL), dried (Na2SO4), and evaporated to give 9a (0.68 g, 99%) as a pale yellow foam; 1NMR (CDCl3) major rotamer δ 9.68 (s, 1 H), 8.97 (dd, J=4.2, 1.5 Hz, 1 H), 8.51 (dd, J=8.6, 1.5 Hz, 1 H), 7.53 (dd, J=8.6, 4.2 Hz, 1 H), 7.47–7.55 (m, 2 H), 7.25–7.40 (m, 3 H), 6.87 (br s, 1 H), 5.49 (s, 2 H), 4.17 (br dt, J=14.5, 7.1 Hz, 1 H), 3.59 (dt, J=14.5, 6.5 Hz, 1 H), 2.57 (br dd, J=7.1, 6.5 Hz, 2 ), 1.23 (s, 9 H); 13C NMR (CDCl3) major rotamer δ 200.3, 154.8, 153.4, 150.0, 143.0, 141.0, 139.7, 135.9, 131.0, 128.6, 127.9, 127.0, 123.4, 112.1, 93.1, 80.7, 70.7, 42.9, 42.5, 27.9; C24H25IN2O4 requires M+. 532.0859. Found 532.0862. 6-[N-(3-Acetoxy-2-propenyl)-N-(tert-butyloxycarbonyl)amino]-8-benzyloxy-5-iodoquinoline (10a). A mixture of 9a (0.62 g, 1.16 mmol), Et3N (0.40 mL, 2.87 mmol), Ac2O (0.25 mL, 2.65 mmol), DMAP (14 mg, 0.11 mmol), and THF (12 mL) was stirred at reflux for 2 h. Further Et3N (0.80 mL, 5.74 mmol), Ac2O (0.50 mL, 5.3 mmol), and DMAP (10 mg, 0.08 mmol) were added and heating was continued for a further 2 h. The solvent was evaporated, and the residue was diluted with pH 7.4 phosphate buffer (50 mL) and extracted with EtOAc (3×20 mL). The combined extracts were washed with water (50 mL), dilute aqueous NaHCO3 (50 mL), and water (50 mL) before being dried (brine, Na2SO4), and evaporated. The residue was purified by dry-flash column chromatography (silica gel, 10–80% EtOAc-hexane) to give 10a (0.54 g, 81%) as a white foam, which contained a 1:4 mixture of Z and E isomers: 1H NMR (CDCl3) major rotamer δ 8.94 (br s, 1 H), 7.45–7.55 (m, 3 H), 7.27–7.40 (m, 3 H), 6.84–7.12 (m, 2 H), 5.36–5.58 (m, 2.8 H), 4.91 (ddd, J=7.6, 6.5, 5.9 Hz, 0.2 H), 4.57 (dd, J=15.0, 5.9 Hz, 0.2 H), 4.39 (dd, J=14.7, 6.8 Hz, 0.8 H), 4.06 (dd, J=15.0, 7.6 Hz, 0.2 H), 3.86 (dd, J=14.7, 7.9 Hz, 0.8 H), 2.08 (s, 2.4 H), 1.88 (s, 0.6 H), 1.57 (br s, 1.8 H), 1.26 (br s, 7.2 H); 13C NMR (CDCl3) major rotamer δ 167.4, 167.0, 154.5, 149.8, 154.3, 149.8, 153.3, 153.1,142.8, 140.9, 139.7, 138.8, 139.7, 143.1, 135.8, 130.9, 136.0, 127.8, 126.8, 126.7, 128.4, 123.2, 112.1, 112.0, 109.1, 108.2, 93.5, 93.1, 80.9, 80.4, 70.8, 70.7, 46.4, 42.7, 27.9, 28.1, 20.3, 20.1; C26H27IN2O5 requires M+. 574.0965. Found 574.0962. 1-(Acetoxymethyl)-5-benzyloxy-3-(tert-butyloxycarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (11). A solution of 10a (0.54 g, 0.94 mmol), AIBN (15 mg, 0.09 mmol), and Bu3SnH (0.32 g, 1.13 mmol) in benzene (45 mL) was stirred at reflux under nitrogen for 5.5 h. The solvent was evaporated, the residue was triturated with pentane, and the precipitate was collected by filtration to give 11 (0.32 g, 77%), which crystallized from MeOH as fluorescent pale yellow rectangular plates: mp 172–173° C.; 1H NMR (CDCl3) δ 8.82 (dd, J=4.1, 1.4 Hz, 1 H), 8.14 (dd, J=8.4, 1.4 Hz, 1 H), 8.07 (br S, 1 H), 7.55 (br s, 2 H), 7.41 (dd, J=8.4, 4.1 Hz, 1 H), 7.36 (dd, J=7.3,7.3 Hz, 2 H), 7.30 (tt, J=7.3, 2.4 Hz, 1 H), 5.44, 5.39 (2×d, J=12.5 Hz, 1 H each), 4.42–4.52 (m, 1 H), 4.05–4.14 (m, 2 H), 3.82–3.93 (m, 2 H), 2.08 (s, 3 H), 1.57 (s, 9 H); 13C NMR (CDCl3) δ 171.0, 155.2, 152.3, 146.9, 142.0 (br), 137.0, 136.3, 131.1, 128.5, 127.9, 127.7, 126.0, 122.1, 113.3 (v. br), 100.4 (br), 81.4 (br), 70.7, 65.8, 52.6, 37.7, 28.4, 20.9. Anal. Calcd for C26H28N2O5: C, 69.63; H, 6.29; N, 6.25. Found: C, 69.46; H, 6.27; N, 6.30. 5-Benzyloxy-3-(tert-butyloxycarbonyl)-1-(hydroxymethyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (12). A mixture of 11 (0.22 g, 0.50 mmol), Cs2CO3 (0.42 g, 1.29 mmol), and EtOH-water (2:1, 6 mL) was stirred at reflux for 30 min. The mixture was diluted with EtOAc (30 mL) and dilute aqueous NaHCO3 (50 mL). The separated aqueous phase was extracted with EtOAc (30 mL). The combined extracts were washed with water (3×50 mL), dried (brine, Na2SO4), and evaporated to give 12 (0.19 g, 95%), which crystallized from MeOH as tiny white needles: mp 170–171° C.; 1H NMR (CDCl3) δ 8.54 (br s, 1 H), 7.99 (br d, J=8.0 Hz, 1 H), 7.91 (br s, 1 H), 7.55 (d, J=6.6 Hz, 2 H), 7.20–7.40 (m, 4 H), 5.29 (s, 2 H), 4.00–4.22 (m, 2 H), 3.65–3.78 (m, 3 H, H-1), 3.23 (br s, 1 H), 1.56 (s, 9 H); 13C NMR (CDCl3) δ 154.4, 152.5 (br), 146.2 (br), 142.2 (v. br), 136.3, 136.2, 131.3, 128.5, 128.0 (v. br), 127.9, 125.9, 121.6, 114.7 (v. br), 100.4 (br), 81.0 (br), 70.7, 64.6, 52.3, 40.9 (br), 28.4. Anal. Calcd. for C24H26N2O4.H2O: C, 67.91; H, 6.65; N, 6.60. Found: C, 68.16; H, 6.47; N, 6.71. 5-Benzyloxy-1-(methylsulfonyloxymethyl)-3-(tert-butyloxycarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (13). MsCl (0.06 mL, 0.7 mmol) was added to a cooled (ice-water) solution of 12 (0.17 g, 0.41 mmol) and Et3N (0.2 mL, 1.4 mmol) in CH2Cl2 (3 mL) and the mixture was stirred for 30 min. The CH2Cl2 was evaporated and the residue was stirred with water (25 mL) for 10 min. The mixture was extracted with EtOAc (2×25 mL). The combined extracts were washed with water (2×50 mL), dried (Na2SO4), and evaporated to give 13 (0.17 g, 86%), which crystallized from MeOH as tiny cream needles: mp 156–157° C.; 1H NMR (CDCl3) δ 8.80 (dd, J=4.2, 1.4 Hz, 1 H), 8.02 (dd, J=8.7, 1.4 Hz, 1 H 7.97 (br s, 1 H), 7.55 (br d, J=6.9 Hz, 2 H), 7.41 (dd, J=8.7, 4.2 Hz), 7.25–7.38 (m, 3 H), 5.40 (s, 2 H), 4.46 (dd, J=9.8, 3.7 Hz, 1 H), 3.93–4.24 (m, 4 H), 2.90 (s, 3 H), 1.57 (s, 9 H); 13C NMR (CDCl3) δ 155.6, 152.1, 147.0, 141.0 (v. br), 137.1, 136.1, 130.5, 128.4, 127.9, 127.6 (br), 125.7, 122.3, 112.7 (v. br), 100.3, 81.6 (br), 70.7, 69.9, 52.0, 38.2 (br), 37.4, 28.3. Anal. Calcd for C25H28N2O6S: C, 61.97; H, 5.82; N, 5.78; S, 6.62. Found: C, 62.15; H, 5.96; N, 5.88; S, 6.54. 5-Benzyloxy-3-(tert-butyloxycarbonyl)-1-(chloromethyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (14). Method 1. A mixture of 13 (50 mg, 0.10 mmol), LiCl (25 mg, 0.59 mmol), and DMF (0.25 mL) was stirred at 80° C. for 1 h, before ice (3 g) was added. The precipitate was removed by filtration, washed with water, and taken up in EtOAc (20 mL). This solution was washed with water (20 mL), dried (Na2SO4), and evaporated to give 14 (39 mg, 89%), which crystallized from MeOH as fluorescent cream needles: mp 178–179° C.; 1H NMR (CDCl3) δ 8.82 (dd, J=4.2, 1.5 Hz, 1 H), 8.05 (br s, 1 H), 7.99 (br d, J=8.4 Hz, 1 H), 7.55 (br s, 2 H), 7.41 (dd, J=8.4, 4.2 Hz, 1 H), 7.35 (dd, J=7.3, 7.3 Hz, 2 H), 7.30 (tt, J=7.3, 2.4 Hz, 1 H), 5.42, 5.38 (2×d, J=12.4 Hz, 1 H each), 4.23 (br d, J=11.7 Hz, 1 H), 4.12 (dd, J=11.7, 8.9 Hz, 1 H), 3.92 (dddd, J=10.1, 8.9, 3.2, 2.6 Hz, 1 H), 3.81 (dd, J=11.1, 3.2 Hz, 1 H), 3.45 (dd, J=11.1, 10.1 Hz, 1 H), 1.56 (s, 9 H); 13C NMR (CDCl3)δ 155.5, 152.3, 146.9, 141.9(br), 137.1, 136.3, 130.3, 128.5, 127.9, 127.7 (br), 125.6, 122.2, 113.4 (v. br), 100.4 (br), 81.6 (br), 70.8, 53.0, 46.3, 41.1, 28.4. Anal. Calcd. for C24H25ClN2O3: C, 67.84; H, 5.93; Cl, 8.34; N, 6.59. Found: C, 67.85; H, 5.94; N, 6.68; Cl, 8.26. 8-Benzyloxy-6-[N-(tert-butyloxycarbonyl)-N-(3-chloro-2-propenyl)amino]-5-iodoquinoline (15a). NaH (60% dispersion in oil, 0.26 g, 6.5 mmol) under nitrogen was washed with pentane (3×2 mL), cooled (ice-water), and treated with a solution of 7a (2.80 g, 5.88 mmol) in DMF (28 mL) over 5 min. The cooling bath was removed and the mixture was allowed to stir for 30 min, by which time the solution was deep yellow and effervescence had ceased. 1,3-Dichloropropene (0.98 g, 8.82 mmol) was added and the mixture was stirred for 86 h The mixture was diluted with water (150 mL) and extracted with EtOAc (4×25 mL). The combined extracts were washed with water (3×100 mL), dried (brine, Na2SO4), and evaporated. The residue was triturated with pentane and the precipitate was collected by filtration to give 15a (3.02 g, 93%) as a tan powder: mp 115–135° C. containing a 1:1 mixture of Z and E isomers; 1H NMR (CDCl3) major rotamer δ 8.95 (br s, 1 H), 8.50 (dd, J=8.4, 2.5 Hz, 1 H), 7.46–7.55 (m, 3 H), 7.27–7.41 (m, 3 H), 6.79–6.96 (m, 1 H), 5.30–6.03 (m, 4 H), 4.54 (dd, J=15.5, 5.6 Hz, 0.5 H), 4.38 (dd, J=14.8, 6.8 Hz, 0.5 H), 4.18 (dd, J=15.5, 6.9 Hz, 0.5 H), 3.79 (dd, J=14.8, 7.8 Hz, 0.5 H), 1.23–1.82 (m, 9 H); 13C NMR (CDCl3) major rotamer δ 154.7, 155.2, 153.6, 153.3, 150.2, 150.1, 143.2, 142.8, 141.2, 140.2, 136.2, 136.0, 131.13, 131.08, 128.79, 128.73, 128.12, 127.99, 127.2, 126.6, 126.98, 126.90, 123.5, 123.4, 122.0, 121.1, 112.2, 111.9, 93.65, 93.58, 80.90, 80.85, 71.0, 70.9, 48.8, 45.4, 28.4, 28.1. C24H24ClIN2O3 requires M+. 550.0520, 552.0491. Found 550.0536, 552.0503. Purification of the mother liquors by dry-flash column chromatography (silica gel, 10–60% EtOAc-hexane) gave further 15a (0.14 g, 4%). Compound 14 by Method 2. A solution of 15a (3.90 g, 5.45 mmol), AIBN (89 mg, 0.54 mmol), and Bu3SnH (1.75 g, 6.0 mmol) in benzene (270 mL) was heated at reflux under nitrogen for 3 h. The benzene was evaporated, the residue was triturated with pentane, and the precipitate was collected by filtration to give 14 (2.21 g, 95%), identical to the material prepared above. Compound 14 by Method 3. A mixture of 12 (19 mg, 0.047 mmol), Ph3P (37 mg, 0.14 mmol) and CH2Cl2 (0.4 mL) was treated with CCl4 (0.05 mL, 0.52 mmol), and the mixture was stirred under nitrogen for 4 h. The mixture was diluted with dilute aqueous NaHCO3 (5 mL) and extracted with EtOAc (3×5 mL). The combined extracts were dried (Na2SO4), evaporated, and purified by dry-flash column chromatography (silica gel, 10–90% EtOAc/hexane) to give 14 (20 mg, 100%) identical with the material prepared above. 3-(tert-Butyloxycarbonyl)-1-(chloromethyl)-5-hydroxy-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (16). A cooled (ice-water) mixture of 14 (0.11 g, 0.27 mmol), 10% Pd/C (55 mg), and TBF (5 mL) under nitrogen was treated with 25% aqueous NH4HCO3 (0.67 mL). The mixture was stirred at 0° C. for 6 h, and was then diluted with EtOAc (20 mL), dried (Na2SO4), filtered through Celite, evaporated, and purified by dry-flash column chromatography (silica gel, 10–50% EtOAc/hexane) to give 16 (39 mg, 44%) as a white solid: mp 148–149° C.; 1H NMR (CDCl3) δ 8.61 (dd, J=4.2, 1.2 Hz, 1 H),8.01 (dd, J=8.5, 1.2 Hz, 1 H), 7.83 (br s, 1 H), 7.41 (dd, J=8.5, 4.2 Hz, 1 H), 4.26 (dd, J=11.8, 2.2 Hz, 1 H), 4.14 (dd, J=11.8, 8.5 Hz, 1 H), 3.93 (dddd, J=9.8, 8.5, 3.2, 2.2 Hz, 1 H), 3.80 (dd, J=11.1, 3.2 Hz, 1 H), 3.46 (dd, J=11.1, 9.8 Hz, 1 H), 1.61 (s, 9 H); 13C NMR (CDCl3) δ 153.5, 152.3, 145.3, 142.4 (br), 135.0, 130.6, 124.9, 122.6, 112.4 (v. br), 100.0, 81.7 (br), 53.0, 46.5, 40.9, 28.4. C17H19ClN2O3 requires M+. 334.1084, 336.1055. Found 334.1081, 336.1058. 5-Benzyloxy-1-(chloromethyl)-3-(5,6,7-trimethoxyindol-2-ylcarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (17a). A suspension of 14 (0.65 g, 1.53 mmol) in dioxane (40 mL) was saturated with HCl, allowed to stand for 1 h, and evaporated. 5,6,7-Trimethoxyindole-2-carboxylic acid (0.38 g, 1.53 mmol), EDCI (0.88 g, 4.6 mmol) and DMA (25 mL) were added to the remaining green-yellow solid, and the red mixture was stirred at room temperature for 39 h. The mixture was poured into a mixture of ice (60 g) and pH 7.4 phosphate buffer (60 mL). The precipitate was removed by filtration, washed with water, and taken up in EtOAc (60 mL). This solution was washed with water (3×50 mL), dried (brine, Na2SO4), and evaporated. The remaining oil was triturated with Et2O. The precipitate was collected by filtration, purified by flash column chromatography (silica gel, EtOAc), and triturated with Et2O to give 17a (0.38 g, 44%) as a pale yellow solid: mp 182–184° C.; 1H NMR (CDCl3) δ 9.59 (s, 1 H), 8.84 (dd, J=4.2, 1.6 Hz, 1 H), 8.37 (s, 1 H), 7.95 (dd, J=8.5, 1.6 Hz, 1 H), 7.58 (br d, J=7.2 Hz, 2 H), 7.38 (dd, J=8.5, 4.2 Hz, 1 H), 7.36 (dd, J=7.3, 7.2 Hz, 2 H), 7.30 (t, J=7.3 Hz, 1 H), 6.93 (d, J=2.2 Hz, 1 H), 6.84 (s, 1 H), 5.48, 5.42 (2×d, J=12.5 Hz, 1 H each), 4.69 (dd, J=10.8, 1.9 Hz, 1 H), 4.57 (dd, J=10.8, 8.5 Hz, 1 H), 4.06, 3.93, 3.90 (3×s, 3 H each), 4.02 (dddd, J=10.3, 8.5, 3.2, 1.9 Hz, 1 H), 3.83 (dd, J=11.4, 3.2 Hz, 1 H), 3.42 (dd, J=11.4, 10.3 Hz, 1 H); 13C NMR (CDCl3) δ 160.5, 155.3, 147.8, 150.2, 142.3, 140.6, 138.8, 138.2, 129.5, 125.1, 123.5, 136.4, 130.4, 128.6, 128.0, 127.7, 125.6, 122.3, 115.3, 106.7, 102.3, 97.6, 70.8, 61.4, 61.1, 56.2, 55.1, 45.9, 42.5. C31H28ClN3O5 requires M+H 558.1796, 560.1766. Found (FAB) 558.1770, 560.1786. Anal. Calcd for C31H28ClN3O5: C, 66.72; H, 5.06; N, 7.53. Found: C, 66.96; H, 5.36; N, 7.50. 1-(Chloromethyl)-5-hydroxy-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (18a). Method 1. THF (10 mL) then 25% aqueous NH4HCO3 (1.1 mL) were added to a cooled (ice-water) mixture of 17a (0.25 g, 0.45 mmol) and 10% Pd/C (0.13 g) under nitrogen. The mixture was stirred at 0° C. for 7.5 h, and was then filtered through Celite. The Celite was washed with a solution of concentrated HCl (2 mL) and MeOH (40 mL) and then with CH2Cl2—MeOH (3:1, 40 mL). The combined filtrates were diluted with water (40 mL) and CH2Cl2 (30 mL) and neutralized with pH 7.4 phosphate buffer. The lower layer was separated then diluted with MeOH (20 mL) and warmed to dissolve the suspended solid. The aqueous phase was extracted with CH2Cl2 (2×20 mL). The extracts were combined, washed with water (100 mL), dried (Na2SO4), and concentrated to a volume of 20 mL. The concentrate was diluted with MeOH (20 mL) and was concentrated to a volume of 10 mL. The precipitate was removed by filtration and washed with MeOH to give 18a (0.14 g, 66%) as a pale yellow microcrystalline solid: mp>230° C.; 1H NMR [(CD3)2SO]δ 11.50 (d, J=2.1 Hz, 1 H), 10.03 (br s, 1 H), 8.76 (dd, J=4.1, 1.3 Hz, 1 H), 8.40 (dd, J=8.4, 1.3 Hz, 1 H), 7.97 (s, 1 H), 7.56 (dd, J=8.4, 4.1 Hz, 1 H), 7.09 (d, J=2.1 Hz, 1 H), 6.97 (s, 1 H), 4.77 (dd, J=11.0, 9.3 Hz, 1 H), 4.48 (dd, J=11.0, 2.0 Hz, 1 H), 4.25 (dddd, J=9.3, 3.9, 3.3, 2.0 Hz, 1 H), 4.03 (dd, J=10.6, 3.3 Hz, 1 H), 3.93, 3.82, 3.80 (3×s, 3 H each), 3.89 (dd, J=10.6, 3.9 Hz, 1 H); 13C NMR ((CD3)2SO) δ 160.3, 153.9, 146.3, 149.1, 142.7, 139.9, 139.0, 136.0, 130.7, 125.4, 124.8, 123.1, 131.6, 122.4, 114.6, 106.2, 102.8, 98.0, 61.0, 60.9, 55.9, 55.0, 47.6, 40.5. Anal. Calcd for C24H22ClN3O5: C, 61.61; H, 4.74; Cl, 7.58; N, 8.98. Found: C, 61.50; H, 4.98; N, 8.84. Compound 18a by Method 2. A solution of 16 (0.14 g, 0.43 mmol) in dioxane (9 mL) was saturated with HCl, allowed to stand for 1 h, and evaporated. 5,6,7-Trimethoxyindole-2-carboxylic acid (0.11 g, 0.43 mmol), EDCI (0.25 g, 1.28 mmol) and DMA (5 mL) were added to the remaining yellow solid, and the red mixture was stirred at room temperature for 22 h. The mixture was poured into a mixture of ice (20 g) and pH 7.4 phosphate buffer (20 mL). The precipitate was removed by filtration, washed with water, and taken up in CH2Cl2—MeOH (2:1, 30 mL). The CH2Cl2 was boiled off, the remaining mixture was cooled in ice, and the precipitate was removed by filtration to give 18a (18 mg, 9%) identical to the material prepared above.