1,1,1-三氟-N-苯基-N-(三氟甲基磺酰基)甲磺酰胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Betuline (2 g, 4.52 mmol) was dissolved in DMF (13 ml) and treated with IMIDAZOLE (0.923 g, 13.55 mmol) and TBDPS-Cl (2.437 ml, 9.49 mmol) at 50° C. for 18 h. TLC showed the reaction was complete. The reaction mixture was cooled to rt and diluted with EtOAc and water. The organic layer was separated dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified using silica gel chromatography (0-20% EtOAc/Hex) to afford (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (2.75 g, 89% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.73 (s, 3H), 0.78 (s, 3H), 0.79 (s, 3H), 0.95 (s, 3H), 0.99 (s, 3H), 1.09 (s, 9H), 0.98-1.66 (m, 19H), 1.67 (s, 3H), 1.80-1.94 (m, 2H), 2.11-2.19 (m, 2H), 2.29 (td, J=11.06, 5.65 Hz, 1H), 3.16-3.24 (m, 1H), 3.35 (d, J=10.07 Hz, 1H), 3.71 (d, J=9.77 Hz, 1H), 3.75-3.81 (m, 1H), 4.55 (s, 1H), 4.62 (d, J=2.14 Hz, 1H), 7.37-7.49 (m, 6H), 7.66-7.75 (m, 4H). Step 2: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (2.75 g, 4.04 mmol) was dissolved in dichloromethane (50 mL) and treated with PCC (1.480 g, 6.86 mmol) at rt for 18 h. The reaction mixture was diluted with 500 mL of 50% EtOAc/Hexane and stirred at rt for 10 min then filtered through a silica gel and celite pad. The solution obtained was concentrated in vacuo and the residue was dissolved in methylene chloride and purified using silica gel (0-20% EtOAc/Hexanes) to afford: (1R,3aS,5aR,5bR,7aR,11aR,11bR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)octadecahydro-1H-cyclopenta[a]chrysen-9(5bH)-one as a white solid (2.5 g, 91%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.77 (S, 3H), 0.89 (s, 3H), 0.97 (s, 3H), 1.05 (s, 3H), 1.09 (s, 12H), 1.13-1.52 (m, 18H), 1.67 (s, 3H), 1.80-1.96 (m, 2H), 2.11-2.22 (m, 2H), 2.29 (td, J=11.04, 5.77 Hz, 1H), 2.35-2.59 (m, 2H), 3.33-3.42 (m, 1H), 3.71 (d, J=9.79 Hz, 1H), 4.56 (s, 1H), 4.62 (d, J=2.01 Hz, 1H), 7.35-7.52 (m, 6H), 7.65-7.78 (m, 4H). Step 3: (1R,3aS,5aR,5bR,7aR,11aR,11bR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)octadecahydro-1H-cyclopenta[a]chrysen-9(5bH)-one (2.5 g, 3.68 mmol) was dissolved in THF (20 mL) and cooled to −78° C. A solution of KHMDS (14.73 mL, 7.36 mmol) in toluene was added and the mixture was stirred at this temperature for 30 min, then N-Phenylbis(trifluoromethane)sulfonimide (1.447 g, 4.05 mmol) was added and the stirring was continued for 3 h. The reaction was quenched with water and extracted with ethylacetate. The organic layers were combined and dried over sodium sulfate, filtered and concentrated. The residue was purified using silica gel (0-20% EtOAc/Hexanes) to afford (1R,3aS,5aR,5bR,7aR,11aR,11bR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl trifluoromethanesulfonate (3.0 g, 3.70 mmol, 100% yield) as a white solid. This compound was taken to the next step without further purification. HPLC: rt=17.6 min (95% water, 5% MeOH, 10 mm Ammonium Acetate; column: Phenomenex Luna C5 4×6×150 mm 5 u; flow: 1 mL/min) Step 4: A mixture of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl trifluoromethanesulfonate (3 g, 3.70 mmol), 4-methoxycarbonylphenylboronic acid (0.998 g, 5.55 mmol), Na2CO3 (1.176 g, 11.10 mmol) and TETRAKIS(TRIPHENYLPHOSPHINE)PALLADIUM(0) (0.128 g, 0.111 mmol) were refluxed in a mixture of Dioxane (8 mL), 2-Propanol (8.00 mL) and Water (5.00 mL) for 18 h. The reaction mixture was diluted with ethyl acetate and water and the organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel to afford methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (1.5 g, 1.882 mmol, 50.9% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.81 (s, 3H), 0.95 (d, J=3.36 Hz, 9H), 1.00 (s, 3H), 1.09 (s, 9H), 1.12-1.66 (m, 18H), 1.69 (s, 3H), 1.81-1.95 (m, 1H), 2.08 (dd, J=17.24, 6.26 Hz, 1H), 2.14-2.23 (m, 2H), 2.31 (td, J=10.99, 5.80 Hz, 1H), 3.37 (d, J=10.07 Hz, 1H), 3.75 (d, J=9.46 Hz, 1H), 3.93 (s, 3H), 4.56 (s, 1H), 4.63 (d, J=1.83 Hz, 1H), 5.27-5.31 (m, 1H), 7.21 (d, J=8.24 Hz, 2H), 7.39-7.52 (m, 6H), 7.66-7.78 (m, 4H), 7.95 (d, J=8.24 Hz, 2H). Step 5: A mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((tert-butyldiphenylsilyloxy)methyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (1.5 g, 1.882 mmol) and tetrabutylammonium fluoride (0.492 g, 1.882 mmol) in THF (15 mL) was heated at 50° C. for 18 h. The reaction quenched with water and diluted with EtOAc. The organic layer was separated, dried over Na2SO4, filtered, concentrated in vacuo and purified on silica gel using 0-50%-EtOAc/Hex to afford methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (838 mg, 1.500 mmol, 80% yield) as a white solid. A portion of 20 mg was further purified using reverse phase prep HPLC for characterization. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.95 (s, 3H), 1.03 (s, 3H), 1.04 (s, 3H), 1.12 (s, 6H), 0.95-2.63 (m, 26H), 3.38 (d, J=10.99 Hz, 1H), 3.80-3.89 (m, 1H), 3.98 (s, 3H), 4.57-4.65 (m, 1H), 4.72 (d, J=2.44 Hz, 1H), 5.25-5.43 (m, 1H), 7.22 (d, J=8.24 Hz, 2H), 7.95 (d, J=8.24 Hz, 2H). then filtered through a silica gel and celite pad The solution obtained was concentrated in vacuo the residue was dissolved in methylene chloride purified to afford cooled to −78° C the mixture was stirred at this temperature for 30 min the stirring was continued for 3 h The reaction was quenched with water extracted with ethylacetate dried over sodium sulfate filtered concentrated The residue was purified

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-chloro-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (450 mg, 1.55 mmol) in DMF (5 mL) was added dropwise to a suspension of sodium hydride (60% dispersion in mineral oil, 74.5 mg, 1.86 mmol) in DMF (5 mL) at room temperature. The mixture was stirred at 40° C. for 30 minutes. The resulting solution was cooled to room temperature and treated with 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (666 mg, 1.86 mmol). The reaction mixture was stirred at room temperature for 1 hour. Next, the solid tert-butyl piperazine-1-carboxylate (636 mg, 3.42 mmol) was added in 2 portions, and the mixture was stirred at 80° C. for 1.5 hours. The mixture was then allowed to cool to room temperature for 18 hours. Saturated NH4Cl solution (30 mL) and water (15 mL) were added, and the mixture was extracted with EtOAc (100 mL). The organic layer was washed with half saturated brine (2×20 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel (Biotage Flash 40 S+) eluting with 15-20%) EtOAc/hexane (step gradient) to provide tert-butyl 4-(5-chloro-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (433 mg, 0.946 mmol, 60.9% yield) as a solid after drying under high vacuum for 18 hours. LCMS (APCI+) m/z 458.1, 460 (M+H)+. The resulting solution was cooled to room temperature The reaction mixture was stirred at room temperature for 1 hour the mixture was stirred at 80° C. for 1.5 hours to cool to room temperature for 18 hours the mixture was extracted with EtOAc (100 mL) The organic layer was washed with half saturated brine (2×20 mL) dried (MgSO4) filtered concentrated in vacuo The resulting residue was purified by flash chromatography on silica gel (Biotage Flash 40 S+) eluting with 15-20%) EtOAc/hexane (step gradient)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydride (0.0881 g, 2.20 mmol) in DMF (5 mL) was added dropwise to 5-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (0.70 g, 1.84 mmol) in DMF (5 mL). Then the reaction mixture was warmed to 40° C. and stirred for 30 minutes. After cooling to room temperature, 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (0.787 g, 2.20 mmol) was added and stirred at room temperature for 1 hour. tert-Butyl piperazine-1-carboxylate (0.787 g, 4.22 mmol) was then added, and the mixture was stirred at 80° C. for 1 hour. Saturated NH4Cl (20 mL) was added, and the reaction was extracted with ethyl acetate and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1) to give tert-butyl 4-(5-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.94 g, 93%) as a solid. MS ESI (+) m/z 550.3 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.64 (s, 1H), 8.31 (s, 1H), 7.20 (d, J=7.6 Hz, 2H), 6.82 (d, J=7.6 Hz, 2H), 5.52 (s, 2H), 3.69 (s, 3H), 3.56 (m, 4H), 3.46 (m, 4H), 1.44 (s, 9H). After cooling to room temperature stirred at room temperature for 1 hour the mixture was stirred at 80° C. for 1 hour the reaction was extracted with ethyl acetate dried over sodium sulfate After removal of the solvent the resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: NaH (0.188 g, 4.70 mmol) in DMF (5 mL) was added dropwise to 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (1.00 g, 3.92 mmol, prepared as described in WO 2007/103308) in DMF (10 mL). The reaction mixture was then warmed to 40° C. and stirred for 30 minutes. After cooling to room temperature, 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.68 g, 4.70 mmol) was added and stirred at room temperature for 1 hour. Then tert-butyl piperazine-1-carboxylate (1.61 g, 8.62 mmol) was added. The mixture was warmed to 80° C. and stirred for 3 hours. The reaction was then cooled to room temperature, and a saturated solution of NH4Cl (30 mL) was added. The mixture was extracted with ethyl acetate (2×30 mL) and dried over sodium sulfate. After removal of solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1) to give tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.64 g, 99% yield) as a solid. MS APCI (+) m/z 424.1 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.24 (s, 1H), 8.13 (d, J=5.2 Hz, 1H), 7.18 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 6.42 (d, J=5.2 Hz, 1H), 5.49 (s, 2H), 3.69 (s, 3H), 3.64 (m, 4H), 3.53 (m, 4H). After cooling to room temperature stirred at room temperature for 1 hour The mixture was warmed to 80° C. stirred for 3 hours The reaction was then cooled to room temperature The mixture was extracted with ethyl acetate (2×30 mL) dried over sodium sulfate After removal of solvent the resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: NaH (0.144 g, 3.59 mmol) in DMF (5 mL) was added dropwise to a solution of 5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (1.00 g, 2.99 mmol) in dimethylformamide (“DMF”) (10 mL). The reaction mixture was warmed to 40° C. and stirred for 30 minutes. After cooling to room temperature, 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.28 g, 3.59 mmol) was added and stirred at room temperature for 1 hour. tert-Butyl piperazine-1-carboxylate (1.23 g, 6.58 mmol) was then added. The mixture was warmed to 80° C. and stirred for 1 hour. The reaction was then cooled to room temperature, and a saturated ammonium chloride solution (30 mL) was added. The reaction mixture was extracted with ethyl acetate (2×20 mL) and dried over sodium sulfate, filtered and concentrated. The resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1) to give tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.23 g, 82%) as a solid. MS ESI (+) m/z 504.3 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.42 (s, 1H), 8.28 (s, 1H), 7.17 (d, J=8.8 Hz, 2H), 6.82 (d, J=8.8 Hz, 2H), 5.48 (s, 2H), 3.66 (s, 3H), 3.49 (m, 8H), 1.40 (s, 9H). After cooling to room temperature stirred at room temperature for 1 hour The mixture was warmed to 80° C. stirred for 1 hour The reaction was then cooled to room temperature The reaction mixture was extracted with ethyl acetate (2×20 mL) dried over sodium sulfate filtered concentrated The resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (10.85 g, 32.5 mmol) in DMF (130 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 1.56 g, 39 mmol) in DMF (70 mL) at room temperature. Once the addition was complete, the mixture was stirred at 40° C. for 30 minutes. The resulting solution was cooled to room temperature and treated with 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (13.92 g, 38.96 mmol). After 1 hour, solid tert-butyl piperazine-1-carboxylate (13.3 g, 71.43 mmol) was added in 2 portions with stirring, and the mixture was stirred at 80° C. for 1.5 hours. The resulting mixture was allowed to cool to room temperature overnight. Saturated NH4Cl solution (100 mL), water (50 mL) and EtOAc (250 mL) were then added to the reaction mixture. The phases were separated, and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phases were washed with water (1×50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was crystallized from boiling EtOAc (˜30 mL) and hexane (˜10 mL). The solid formed was filtered, washed with additional hexane (2×10 mL), and dried to provide tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (14.8 g, 91% yield) as a solid. LCMS (APCI+) m/z 504 (M+H)+, Retention time=4.56 minutes. Once the addition The resulting solution was cooled to room temperature After 1 hour with stirring the mixture was stirred at 80° C. for 1.5 hours to cool to room temperature overnight The phases were separated the aqueous layer was extracted with EtOAc (2×50 mL) The combined organic phases were washed with water (1×50 mL) dried (MgSO4) filtered concentrated in vacuo The residue obtained was crystallized The solid formed was filtered washed with additional hexane (2×10 mL) dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 293 mg of (2S,5S)-2-(t-butyl)-5-phenyl-1,3-dioxolan-4-one, which had been synthesized following the method of D. Seebach, et al. [Tetrahedron, Vol. 40, pp. 1313-1324 (1984)], in 10 ml of tetrahydrofuran, 1.0 ml of a hexane solution of 1.5 M lithium diisopropylamide was added dropwise at -78° C., followed by 30 minutes' stirring, addition of 0.15 ml of cyclopentanone, 1 hour's stirring at the same temperature and then addition of a solution of 510 mg of N-phenyltrifluoromethanesulfonimide in 5 ml of tetrahydrofuran. The reaction mixture was stirred overnight while being restored to room temperature. The resultant reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The extract was washed with saturated saline solution, dried over anhydrous magnesium sulfate and removed of the solvent by reduced pressure distillation. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/1), and 361 mg of an yellow oily substance was obtained, 113 mg of which was dissolved in 4 ml of methanol. To the solution 45 mg of sodium acetate and 15 mg of 10% palladium-on-carbon were added and stirred for 6 hours in a hydrogen atmosphere at normal pressure and room temperature. The reaction mixture was filtered through celite pad and removed of the solvent by reduced pressure distillation. To the residue ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added. The organic layer was separated, washed with saturated saline solution, dried over anhydrous magnesium sulfate and removed of the solvent by reduced pressure distillation. The residue was purified by preparative thin layer chromatography (Kieselgel™ 60F254, Art 5744: Merck, hexane/ethyl acetate=19/1) to give 63 mg of a colorless oily substance. This product was dissolved in 1 ml of methanol, added with 1 ml of 1N sodium hydroxide solution and stirred for 3 hours at 60° C. Distilling the methanol off under reduced pressure, the remaining reaction mixture was washed with diethyl ether, made acidic with 1N hydrochloric acid and extracted with chloroform. The organic layer was washed with saturated saline solution, dried over anhydrous magnesium sulfate and removed of the solvent by reduced pressure distillation, to give 46 mg of the title compound as a white solid. stirring at the same temperature The reaction mixture was stirred overnight while being restored to room temperature The resultant reaction mixture extracted with ethyl acetate The extract was washed with saturated saline solution dried over anhydrous magnesium sulfate removed of the solvent by reduced pressure distillation The residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/1), and 361 mg of an yellow oily substance was obtained The reaction mixture was filtered through celite pad removed of the solvent by reduced pressure distillation To the residue ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added The organic layer was separated washed with saturated saline solution dried over anhydrous magnesium sulfate removed of the solvent by reduced pressure distillation The residue was purified by preparative thin layer chromatography (Kieselgel™ 60F254, Art 5744: Merck, hexane/ethyl acetate=19/1) to give 63 mg of a colorless oily substance stirred for 3 hours at 60° C Distilling the methanol off under reduced pressure the remaining reaction mixture was washed with diethyl ether extracted with chloroform The organic layer was washed with saturated saline solution dried over anhydrous magnesium sulfate removed of the solvent by reduced pressure distillation

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 9-hydroxycamptothecin (9-HC; 300 mg, 0.82 mmol) in N,N-dimethylformamide (15 ml), triethylamine (0.68 ml, 4.92 mmol. 6.0 eq.) and N-phenyl trifluoromethanesulfonimide (879 mg, 2.46 mmol, 3.0 eq.) were added, and the mixture was stirred at 60° C. for 0.5 hr under argon gas atmosphere. After confirmation of the disappearance of the starting material by thin layer chromatography (chloroform:methanol=20:1), this reaction solution was added with triethylamine (1.14 ml, 8.20 mmol. 10.0 eq.), dichlorobis(triphenylphosphine)palladium (58 mg, 0.08 mmol, 10 mol %), formic acid (189 mg, 4.10 mmol, 5.0 eq.) and heated at 60° C. for 3 hr. After the disappearance of 9-OTfC was confirmed by thin layer chromatography (chloroform:methanol=50:1), and the reaction mixture was cooled, followed by evaporation of the solvent under reduced pressure. The residue was added with chloroform (5 ml) and n-hexane (200 ml) and the resulting precipitate was taken by suction filtration to give camptothecin (CPT) (209 mg, yield 73%) as a yellow solid. heated at 60° C. for 3 hr the reaction mixture was cooled followed by evaporation of the solvent under reduced pressure The residue was added with chloroform (5 ml) and n-hexane (200 ml) the resulting precipitate was taken by suction filtration