* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium hydroxide In water; <i>tert</i>-butyl alcohol
Terephthalic acid-mono-t-butyl ester A slurry of terephthalic acid di-tert-butyl ester (6.1 g, 0.022 mole) in tert-butanol (30 mL) was added to 1N KOH (22 mL, 0.022 mole). The mixture was heated to 60° C. for 7-8 hours. After cooling the mixture was treated with water and extracted 3 times with ethyl acetate. The aqueous layer was acidified with dilute HCL and the product was extracted into ethyl acetate. After washing of the organic layer with a saturated aqueous NaCl solution and drying over MgSO4, the solvent was filtered and concentrated to yield terephthalic acid mono tert butyl ester as a white solid (4.7 g, 96percent) melting at 100°-102° C.
96%
With potassium hydroxide In water; <i>tert</i>-butyl alcohol
Terephthalic Acid-Mono-T-Butyl Ester A slurry of terephthalic acid di-tert-butyl ester (6.1 g, 0.022 mole) in tert-butanol (30 mL) was added to 1N KOH (22 mL, 0.022 mole). The mixture was heated to 60° C. for 7-8 hours. After cooling the mixture was treated with water and extracted 3 times with ethyl acetate. The aqueous layer was acidified with diulute HCL and the product was extracted into ethyl acetate. After washing of the organic layer with a saturated aqueous NaCl solution and drying over MgSO4, the solvent was filtered and concentrated to yield terephthalic acid mono tert-butyl ester as a white solid (4.7 g, 96percent) melting at 100°-102° C.
96%
With potassium hydroxide In water; <i>tert</i>-butyl alcohol
Terephthalic acid-mono-t-butyl ester A slurry of terephthalic acid di- tert -butyl ester (6.1 g, 0.022 mole) in tert -butanol (30 mL) was added to 1N KOH (22 mL, 0.022 mole). The mixture was heated to 60°C for 7-8 hours. After cooling the mixture was treated with water and extracted 3 times with ethyl acetate. The aqueous layer was acidified with dilute HCL and the product was extracted into ethyl acetate. After washing of the organic layer with a saturated aqueous NaCl solution and drying over MgSO4, the solvent was filtered and concentrated to yield terephthalic acid mono tert butyl ester as a white solid (4.7 g, 96percent) melting at 100-102°C.
Y: 30%
With potassium hydroxide In diethyl ether; water; <i>tert</i>-butyl alcohol
EXAMPLE 40 Mono-tert-butyl terephthalate (XXVII) STR42 To a solution of potassium hydroxide (255 mg, 4.55 mmol) in 4.0 mL tert-butyl alcohol with 0.5 mL of water added for solubility was added compound XXVI (1.15 g, 4.14 mmol) in tert-butyl alcohol (5.5 mL). After 3 hours at 50° C., diethyl ether (35 mL) was added and the reaction mixture filtered. The solid was dissolved in water (35.0 mL), extracted with methylene chloride (2*50 mL), and then acidified with 1N HCl. The precipitate was then collected to give 270 mg (Y: 30percent) of the title compound; 1 H-NMR (CDCl3): δ8.02 (m, 4H), 1.56 (s, 9H); MS (DCI) m/e: 223 (MH+).
Y: 30%
With potassium hydroxide In diethyl ether; water; <i>tert</i>-butyl alcohol
EXAMPLE 40 Mono-tert-butyl terephthalate (XXVII) STR42 To a solution of potassium hydroxide (255 mg, 4.55 mmol) in 4.0 mL tert-butyl alcohol with 0.5 mL of water added for solubility was added compound XXVI (1.15 g, 4.14 mmol) in tert-butyl alcohol (5.5 mL). After 3 hours at 50° C., diethyl ether (35 mL) was added and the reaction mixture filtered. The solid was dissolved in water (35.0 mL), extracted with methylene chloride (2*50 mL), and then acidified with 1N HCl. The precipitate was then collected to give 270 mg (Y: 30percent) of the title compound; 1 H-NMR (CDCl3): δ 8.02 (m, 4H), 1.56 (s, 9H); MS (DCI) m/e: 223 (MH+).
Reference：
[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 4, p. 641 - 662
[2] Patent: US5221665, 1993, A,
[3] Patent: US5232928, 1993, A,
[4] Patent: EP369391, 1991, A3,
[5] Patent: EP369391, 1990, A2,
[6] Journal of Medicinal Chemistry, 2000, vol. 43, # 21, p. 3852 - 3861
[7] Organic and Biomolecular Chemistry, 2011, vol. 9, # 22, p. 7791 - 7798
[8] Revue Roumaine de Chimie, 1991, vol. 36, # 1-3, p. 171 - 186
[9] Patent: US5618839, 1997, A,
[10] Patent: US5648385, 1997, A,
2
[ 100-21-0 ]
[ 24424-99-5 ]
[ 20576-82-3 ]
Yield
Reaction Conditions
Operation in experiment
16.7%
With dmap In tetrahydrofuran; <i>tert</i>-butyl alcohol for 24 h; Reflux
Terephthalic acid (25) (1.66 g), di-tert-butyl dicarbonate (2.18 g) and 4-dimethylaminopyridine (305 mg) were added to a mixed solution of t-butanol (15 mL) / tetrahydrofuran ,And heated under reflux for 24 hours.After returning to room temperature, the reaction solution was concentrated under reduced pressure and the obtained residue was purified by silica gel flash column chromatography (developing solvent: chloroform: methanol = 20: 1) to give the title compound (26) (371 mg, yield 16.7 percent) As a white solid.
Reference：
[1] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3524 - 3548
[2] Patent: JP2017/71567, 2017, A, . Location in patent: Paragraph 0183-0184; 0188
3
[ 65874-27-3 ]
[ 20576-82-3 ]
Reference：
[1] Journal of Medicinal Chemistry, 2001, vol. 44, # 10, p. 1491 - 1508
With potassium hydroxide; In water; tert-butyl alcohol;
Terephthalic acid-mono-t-butyl ester A slurry of terephthalic acid di-tert-butyl ester (6.1 g, 0.022 mole) in tert-butanol (30 mL) was added to 1N KOH (22 mL, 0.022 mole). The mixture was heated to 60 C. for 7-8 hours. After cooling the mixture was treated with water and extracted 3 times with ethyl acetate. The aqueous layer was acidified with dilute HCL and the product was extracted into ethyl acetate. After washing of the organic layer with a saturated aqueous NaCl solution and drying over MgSO4, the solvent was filtered and concentrated to yield terephthalic acid mono tert butyl ester as a white solid (4.7 g, 96%) melting at 100-102 C.
96%
With potassium hydroxide; In water; tert-butyl alcohol;
Terephthalic Acid-Mono-T-Butyl Ester A slurry of terephthalic acid di-tert-butyl ester (6.1 g, 0.022 mole) in tert-butanol (30 mL) was added to 1N KOH (22 mL, 0.022 mole). The mixture was heated to 60 C. for 7-8 hours. After cooling the mixture was treated with water and extracted 3 times with ethyl acetate. The aqueous layer was acidified with diulute HCL and the product was extracted into ethyl acetate. After washing of the organic layer with a saturated aqueous NaCl solution and drying over MgSO4, the solvent was filtered and concentrated to yield terephthalic acid mono tert-butyl ester as a white solid (4.7 g, 96%) melting at 100-102 C.
96%
With potassium hydroxide; In water; tert-butyl alcohol;
Terephthalic acid-mono-t-butyl ester A slurry of terephthalic acid di- tert -butyl ester (6.1 g, 0.022 mole) in tert -butanol (30 mL) was added to 1N KOH (22 mL, 0.022 mole). The mixture was heated to 60C for 7-8 hours. After cooling the mixture was treated with water and extracted 3 times with ethyl acetate. The aqueous layer was acidified with dilute HCL and the product was extracted into ethyl acetate. After washing of the organic layer with a saturated aqueous NaCl solution and drying over MgSO4, the solvent was filtered and concentrated to yield terephthalic acid mono tert butyl ester as a white solid (4.7 g, 96%) melting at 100-102C.
270 mg (Y: 30%)
With potassium hydroxide; In diethyl ether; water; tert-butyl alcohol;
EXAMPLE 40 Mono-tert-butyl terephthalate (XXVII) STR42 To a solution of potassium hydroxide (255 mg, 4.55 mmol) in 4.0 mL tert-butyl alcohol with 0.5 mL of water added for solubility was added compound XXVI (1.15 g, 4.14 mmol) in tert-butyl alcohol (5.5 mL). After 3 hours at 50 C., diethyl ether (35 mL) was added and the reaction mixture filtered. The solid was dissolved in water (35.0 mL), extracted with methylene chloride (2*50 mL), and then acidified with 1N HCl. The precipitate was then collected to give 270 mg (Y: 30%) of the title compound; 1 H-NMR (CDCl3): delta8.02 (m, 4H), 1.56 (s, 9H); MS (DCI) m/e: 223 (MH+).
270 mg (Y: 30%)
With potassium hydroxide; In diethyl ether; water; tert-butyl alcohol;
EXAMPLE 40 Mono-tert-butyl terephthalate (XXVII) STR42 To a solution of potassium hydroxide (255 mg, 4.55 mmol) in 4.0 mL tert-butyl alcohol with 0.5 mL of water added for solubility was added compound XXVI (1.15 g, 4.14 mmol) in tert-butyl alcohol (5.5 mL). After 3 hours at 50 C., diethyl ether (35 mL) was added and the reaction mixture filtered. The solid was dissolved in water (35.0 mL), extracted with methylene chloride (2*50 mL), and then acidified with 1N HCl. The precipitate was then collected to give 270 mg (Y: 30%) of the title compound; 1 H-NMR (CDCl3): delta 8.02 (m, 4H), 1.56 (s, 9H); MS (DCI) m/e: 223 (MH+).
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-2-methyl-1-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-propyl)-benzamide[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-2-methyl-1-{methyl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-propyl)-benzamide[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-1-{cycloheptyl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-benzamide[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-1-{furan-2-ylmethyl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-benzamide[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-2-methyl-1-{(tetrahydro-furan-2-ylmethyl)-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-propyl)-benzamide[ No CAS ]
N-((S)-1-{Benzyl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-4-(4-chloro-benzenesulfonylaminocarbonyl)-benzamide[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-1-{cyclooctyl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-benzamide[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-1-{indan-2-yl-[(3,3,3-trifluoro-2-hydroxy-1-methyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-benzamide[ No CAS ]
4-(4-Bromo-benzenesulfonylaminocarbonyl)-N-((S)-1-{indan-2-yl-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-benzamide[ No CAS ]
2-{(S)-2-[4-(4-Chloro-benzenesulfonylaminocarbonyl)-benzoylamino]-3-methyl-butyryl}-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (3,3,3-trifluoro-2-hydroxy-1-isopropyl-propyl)-amide[ No CAS ]
4-{{(S)-2-[4-(4-Chloro-benzenesulfonylaminocarbonyl)-benzoylamino]-3-methyl-butyryl}-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-amino}-piperidine-1-carboxylic acid ethyl ester[ No CAS ]
4-(4-Chloro-benzenesulfonylaminocarbonyl)-N-((S)-1-[2-(3,4-dimethoxy-phenyl)-ethyl]-[(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propylcarbamoyl)-methyl]-carbamoyl}-2-methyl-propyl)-benzamide[ No CAS ]
EXAMPLE 2 Synthesis of mono-tert-butyl terephthalate In the same manner as in Example 1, 10 g (0.056 mol) of monomethyl terephthalate and 200 ml (2.081 mols) of tert-butyl alcohol were charged, and 8.10 g (0.070 mol, 1.3 equivalent) of potassium-tert-butoxide was poured thereinto little by little at room temperature. As a result, the reaction mixture generated heat to result in rising of the temperature to 35 C., and white crystals were precipitated in the reaction mixture. Thereafter, the reaction mixture was heated to 83 C. and the reaction was carried out for 17 hours, during which methyl alcohol produced by the transesterification was distilled off together with tert-butyl alcohol, and tert-butyl alcohol in the same amount as the amount of the distilled tert-butyl alcohol was continuously added through the dropping funnel. After completion of the transesterification, tert-butyl alcohol was distilled off under normal pressure, and the residue was allowed to stand for cooling. Then, 80 ml of ice water was added to the residue, followed by separation washing twice with 100 ml of n-hexane. To the resulting aqueous phase was added 3.85 g (0.036 mol, 1.4 equivalent) of sulfuric acid diluted with 20 ml of cold water to liberate the acid. The components in the aqueous phase were analyzed by GC to obtain a peak area ratio of 66:34 of the starting monomethyl terephthalate and the product mono-tert-butyl terephthalate. This aqueous phase was subjected to extraction twice with 100 ml of n-hexane, and then the n-hexane phase extracted twice was washed thrice with 10 ml of pure water and thereafter subjected to concentration under reduced pressure. As a result, 2.99 g of mono-tert-butyl terephthalate of 94% in purity containing no monomethyl terephthalate was obtained. The yield in this case was 23%. Spectrum data of 1H-NMR on the product were as follows. 1H-NMR(CDCl3) 1.62 (9H, s), 8.08 (2H, d, J=8.1 Hz), 8.16 (2H, d, J=8.1 Hz).
78
[ 20576-82-3 ]
[ 541-41-3 ]
[ 554-68-7 ]
Yield
Reaction Conditions
Operation in experiment
With triethylamine; In tetrahydrofuran;
Reference Example 5 p-(t-Butoxycarbonyl)benzaldehyde STR32 To a solution of p-(t-butoxycarbonyl)benzoic acid (13.32 g) in tetrahydrofuran (100 ml) and triethylamine (10 ml), was added slowly dropwise ethyl chloroformate (6.8 ml) under cooling with ice, under an atmosphere of argon. After the mixture was stirred for two hours at room temperature, triethylamine,hydrochloride precipitated was filtered off.
EXAMPLE 41 4-[[(5,6-Dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl)oxy]carbonyl]benzoic acid, tert-butyl ester (I7 a) STR43 To a solution of compound XXVII (107 mg, 0.480 mmol) in methylene chloride (5 mL) at 0 C. was added oxalyl chloride (0.15 mL) and dimethylformamide (2 drops). After 2 hours at room temperature, the reaction mixture was concentrated in vacuo to give the corresponding acid chloride (compound XXIVa). To a solution of compound XXIVa (0.480 mmol) in dry pyridine (5 mL) was then added compound XXVa (120 mg, 0.48 mmol). After 16 hours at room temperature, the mixture was diluted with 1N HCl, extracted with ethyl acetate (100 mL), washed with 1N HCl (4*100 mL), and washed with saturated sodium bicabonate (2*100 mL). The organic phase was then separated, dried over magnesium sulfate and concentrated in vacuo to give 137 mg (Y: 63%) of the title compound; 1 H-NMR (CDCl3) delta8.16 (d, J=8.4 Hz, 2H), 8.06 (d, J=8.4 Hz, 2H), 7.35 (m, 6H), 7.07 (dd, J=8.4 Hz, 2.4 Hz, 1H), 6.84 (d, J=2.4 Hz, 1H), 6.04 (t, J=4.6 Hz, 1H), 2.38 (d, J=4.6 Hz, 2H), 1.61. (s, 9H), 1.36 (s, 6H); MS (DCI) m/e: 455 (MH+).
137 mg (Y: 63%)
In pyridine; N-methyl-acetamide; dichloromethane;
EXAMPLE 41 4-[[(5,6-Dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl)oxy]carbonyl]benzoic acid, tert-butyl ester (I7 a) STR43 To a solution of compound XXVII (107 mg, 0.480 mmol) in methylene chloride (5 mL) at 0 C. was added oxalyl chloride (0.15 mL) and dimethylformamide (2 drops). After 2 hours at room temperature, the reaction mixture was concentrated in vacuo to give the corresponding acid chloride (compound XXIVa). To a solution of compound XXIVa (0.480 mmol) in dry pyridine (5 mL) was then added compound XXVa (120 mg, 0.48 mmol). After 16 hours at room temperature, the mixture was diluted with 1N HCl, extracted with ethyl acetate (100 mL), washed with 1N HCl (4*100 mL), and washed with saturated sodium bicarbonate (2*100 mL). The organic phase was then separated, dried over magnesium sulfate and concentrated in vacuo to give 137 mg (Y: 63%) of the title compound; 1 H-NMR (CDCl3) delta 8.16 (d, J=8.4 Hz, 2H), 8.06 (d, J=8.4 Hz, 2H), 7.35 (m, 6H), 7.07 (dd, J=8.4 Hz, 2.4 Hz, 1H), 6.84 (d, J=2.4 Hz, 1H), 6.04 (t, J=4.6 Hz, 1H), 2.38 (d, J=4.6 Hz, 2H), 1.61. (s, 9H), 1.36 (s, 6H); MS (DCI) m/e: 455 (MH+).
4,4-dimethyl-7-mercapto-1-tetralone (XLIII)[ No CAS ]
[ 20576-82-3 ]
4-[[[(5,6,7,8-Tetrahydro-5,5-dimethyl-8-oxo)-2-naphthalenyl]sulfamyl]carbonyl]benzoic acid, t-butyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80 mg (Y: 35%)
In pyridine; hexane; dichloromethane; N,N-dimethyl-formamide;
EXAMPLE 72 4-[[[(5,6,7,8-Tetrahydro-5,5-dimethyl-8-oxo)-2-naphthalenyl]sulfamyl]carbonyl]benzoic acid, t-butyl ester (XLIVa) STR73 To a solution of mono-tert-butylterephthalate (122 mg, 0.550 mmol) in anhydrous methylene chloride (5.0 mL) was added oxalyl chloride (0.17 mL, 1.95 mmol) and 2 drops of N,N-dimethylformamide at 0 C. After being stirred at room temperature for 2 hours, the mixture was concentrated in vacuo. The residue was dissolved in anhydrous pyridine (5.0 mL) to which was added 4,4-dimethyl-7-mercapto-1-tetralone (XLIII) (113 mg, 0.550 mmol). After 2 hours at room temperature, the mixture was diluted with 1N HCl, extracted with ethyl acetate (50 mL), washed with 1N HCl (3*50 mL) and washed with saturated sodium bicarbonate (2*50 mL). The organic phase was then separated and concentrated in vacuo. The residue was chromatographed on silica gel (eluted with 10% ethyl acetate in hexane) to give 80 mg (Y: 35%) of the title product; 1 H-NMR (CDCl3): delta8.16 (d, J=1.8 Hz, 1H), 8.11-8.03 (m, 4H), 7.67 (dd, J=8.3, 2.1 Hz, 1H), 7.54 (d, J=8.5 Hz, 1H), 2.77 (t, J=6.8 Hz, 2H), 2.06 (t, J=6.8 Hz, 2H), 1.63 (s, 9H), 1.44 (s, 6H); MS (DCI) m/e: 355 (M-C4 H9 +H)+.
80 mg (Y: 35%)
In pyridine; hexane; dichloromethane; N,N-dimethyl-formamide;
EXAMPLE 72 4-[[[(5,6,7,8-Tetrahydro-5,5-dimethyl-8-oxo)-2-naphthalenyl]sulfamyl]carbonyl]benzoic acid, t-butyl ester (XLIVa) STR73 To a solution of mono-tert-butylterephthalate (122 mg, 0.550 mmol) in anhydrous methylene chloride (5.0 mL) was added oxalyl chloride (0.17 mL, 1.95 mmol) and 2 drops of N,N-dimethylformamide at 0 C. After being stirred at room temperature for 2 hours, the mixture was concentrated in vacuo. The residue was dissolved in anhydrous pyridine (5.0 mL) to which was added 4,4-dimethyl-7-mercapto-1-tetralone (XLIII) (113 mg, 0.550 mmol). After 2 hours at room temperature, the mixture was diluted with 1N HCl, extracted with ethyl acetate (50 mL), washed with 1N HCl (3*50 mL) and washed with saturated sodium bicarbonate (2*50 mL). The organic phase was then separated and concentrated in vacuo. The residue was chromatographed on silica gel (eluted with 10% ethyl acetate in hexane) to give 80 mg (Y: 35%) of the title product; 1 H-NMR (CDCl3): delta 8.16 (d, J=1.8 Hz, 1H), 8.11-8.03 (m, 4H), 7.67 (dd, J=8.3, 2.1 Hz, 1H), 7.54 (d, J=8.5 Hz, 1H), 2.77 (t, J=6.8 Hz, 2H), 2.06 (t, J=6.8 Hz, 2H), 1.63 (s, 9H), 1.44 (s, 6H); MS (DCI) m/e: 355 (M-C4 H9 +H)+.
a. 1,1-Dimethylethyl 4-[(4-chlorophenyl)sulfonylaminocarbonyl]benzoate A 5-liter 3-neck round bottom flask was equipped with a mechanical stirrer and nitrogen inlet. CH2 Cl2 (2 liters) was placed in the reaction flask and terephthalic acid mono-t-butyl ester (127.5 g, 0.574 mol), DMAP (70.06 g, 0.574 mol), and 4-chlorobenzenesulfonamide (110.04 g, 0.574 mol) were added in that order using CH2 Cl2 (400 ml) to wash down the solids. WSCDI (110.10 g, 0.574 mol) was added in portions over 10 min using CH2 Cl2 (100 ml) to wash down the solid. After the reaction mixture was stirred overnight at room temperature, it was concentrated under vacuum to dryness. The residue was partioned between EtOAc and water. The EtOAc solution was washed (20% aq citric acid, satd aq NaHCO3, brine), dried (Na2 SO4), and concentrated under vacuum to a white solid. After drying in a vacuum oven at 50, the title product (227 g, 100%) was obtained in a sufficiently pure state to be used directly for the next step; TLC, Rf =0.43, MeOH:CHCl3 (15:85). (Further purification was possible by recrystallization from EtOH:water; m.p. above 300).
4-(Phenylsulfonylaminocarbonyl)benzoic acid t-butyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; dmap; In ethanol; dichloromethane; ethyl acetate;
c. 4-(Phenylsulfonylaminocarbonyl)benzoic acid t-butyl ester WSCDI (9.49 g) and then the product of Example 21b (10.0 g) were added to a stirred solution of DMAP (6.05 g) and benzenesulfonamide (7.07 g) in CH2 Cl2 (500 ml). The reaction was stirred at room temperature overnight, filtered, the filtrate concentrated under vacuum and the residue dissolved in EtOAc. The organic solution was washed (1M aqueous HCl, saturated aqueous NaHCO3 and brine), dried (MgSO4) and concentrated. The sticky residue was dissolved in ethanol, and H2 O was added until the product precipitated. The precipitate was filtered and dried to give the product as a white powder (9.75 g); mp 141-143.
With dmap; dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; for 72h;
To 2-pyridin-3-yl-1 H-indole-5-carbonitrile (575 mg, 2.62 mmol), 4- (butoxycarbonyl)benzoic acid (700 mg, 3.15 mmol) and DMAP (780 mg, 3.93 mmol) in DMF (30 mL) is added DCC (811 mg, 3.93 mmol). The reaction is stirred for 3 days and the mixture is poured into water (50 mL) and extracted with ethyl acetate, dried over Na2SO4 and concentrated. The residue is purified by silica gel flash chromatography (ethyl acetate-heptane gradient) to give 4-(5-cyano-2-pyridin-3-yl-indole-1-carbonyl)- benzoic acid tert-butyl ester as a white solid. MS (ESI) m/z 424 (M+H)+.
With dmap; In tetrahydrofuran; tert-butyl alcohol; for 24h;Reflux;
Terephthalic acid (25) (1.66 g), di-tert-butyl dicarbonate (2.18 g) and 4-dimethylaminopyridine (305 mg) were added to a mixed solution of t-butanol (15 mL) / tetrahydrofuran ,And heated under reflux for 24 hours.After returning to room temperature, the reaction solution was concentrated under reduced pressure and the obtained residue was purified by silica gel flash column chromatography (developing solvent: chloroform: methanol = 20: 1) to give the title compound (26) (371 mg, yield 16.7 %) As a white solid.
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