* 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.
In 3-hydroxy-5-nitrobenzoic acid (5.9 kg, 32.2 mol), methanol (60 L) was added, and sulfuric acid (375 ml, catalytic amount) was slowly added thereto, followed by refluxing and stirring at 80° C. for 18 hours. After completing the reaction, the reactant was cooled to room temperature. Purified water (50 L) was added thereto, and methanol was distilled off under a reduced pressure. The solid thus produced was stirred at 10° C. for 1 hour and filtered. The filtrant was washed with purified water, and dried at 60° C. to obtain the title compound (5.52 kg, yield: 87percent, yellow solid). 1H-NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.04 (s, 1H), 7.74 (s, 1H), 7.66 (s, 1H), 3.88 (s, 3H)
3.9 g
at 0 - 6℃; for 3 h;
o a solution of 3-hydroxy-5-nitrobenzoic acid (3.7 g, 20.00 mmol) in MeOH (70.0 mL), SOCl2(12.0 mL) was added at 0°C. The reaction mixture was stirred at 6°C for 3 hours, and concentrated under reduced pressure. Water was added to the residue, followed by extracting with EtOAc. The organic extract was washed with brine, dried over anhydrous Na2S04, concentrated under reduced pressure to obtain methyl 3-hydroxy- 5-nitrobenzoate (3.9 g) as an off-white solid without purification.1H-NMR (300MHz, DMSO-d6) δ 10.96 (s, 1H), 8.08 (m, 1H), 7.78 (m, 1H), 7.70 (m, 1H), 3.90 (s, 3H)
Reference:
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4812 - 4830
[2] Patent: US2014/350007, 2014, A1, . Location in patent: Paragraph 0076; 0077; 0078
[3] Journal of Medicinal Chemistry, 1984, vol. 27, # 12, p. 1549 - 1559
[4] Patent: US2010/69431, 2010, A1, . Location in patent: Page/Page column 110-111
[5] Patent: WO2014/196793, 2014, A1, . Location in patent: Page/Page column 74
[6] Angewandte Chemie - International Edition, 2016, vol. 55, # 27, p. 7821 - 7825[7] Angew. Chem., 2016, vol. 128, p. 7952 - 7956,5
2
[ 78238-14-9 ]
[ 55076-32-9 ]
Reference:
[1] Patent: US2002/165275, 2002, A1,
3
[ 78238-14-9 ]
[ 193693-95-7 ]
Reference:
[1] Journal of the American Chemical Society, 2005, vol. 127, # 32, p. 11202 - 11203
4
[ 78238-14-9 ]
[ 77-78-1 ]
[ 78238-12-7 ]
[ 78238-13-8 ]
Reference:
[1] Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, # 2, p. 313 - 317[2] Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 2, p. 369 - 374
[3] Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, # 2, p. 313 - 317[4] Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 2, p. 369 - 374
5
[ 78238-14-9 ]
[ 77-78-1 ]
[ 78238-12-7 ]
Reference:
[1] Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 11, p. 4092 - 4101
6
[ 78238-14-9 ]
[ 76045-71-1 ]
Reference:
[1] Australian Journal of Chemistry, 1981, vol. 34, # 6, p. 1319 - 1324
[2] Organic Letters, 2009, vol. 11, # 4, p. 791 - 794
[3] Chemistry - A European Journal, 2011, vol. 17, # 2, p. 613 - 619
7
[ 78238-12-7 ]
[ 78238-14-9 ]
Reference:
[1] Journal of the American Chemical Society, 2005, vol. 127, # 32, p. 11202 - 11203
[2] Organic Letters, 2009, vol. 11, # 4, p. 791 - 794
[3] Synthesis (Germany), 2016, vol. 48, # 19, p. 3263 - 3271
[4] Patent: EP2364983, 2011, A2, . Location in patent: Page/Page column 77
[5] Patent: US2011/218193, 2011, A1, . Location in patent: Page/Page column 66
8
[ 99-34-3 ]
[ 78238-14-9 ]
Reference:
[1] Journal of the American Chemical Society, 2005, vol. 127, # 32, p. 11202 - 11203
[2] Journal of Medicinal Chemistry, 1984, vol. 27, # 12, p. 1549 - 1559
[3] Patent: EP2364983, 2011, A2,
[4] Patent: US2011/218193, 2011, A1,
[5] Synthesis (Germany), 2016, vol. 48, # 19, p. 3263 - 3271
9
[ 618-84-8 ]
[ 78238-14-9 ]
Reference:
[1] Chemistry - A European Journal, 2011, vol. 17, # 2, p. 613 - 619
[2] Recueil des Travaux Chimiques des Pays-Bas, 1921, vol. 40, p. 625
[3] Journal of Medicinal Chemistry, 1984, vol. 27, # 12, p. 1549 - 1559
10
[ 78238-13-8 ]
[ 78238-14-9 ]
Reference:
[1] Australian Journal of Chemistry, 1981, vol. 34, # 6, p. 1319 - 1324
11
[ 2702-58-1 ]
[ 78238-14-9 ]
Reference:
[1] Australian Journal of Chemistry, 1981, vol. 34, # 6, p. 1319 - 1324
12
[ 78238-14-9 ]
[ 14206-69-0 ]
Reference:
[1] Organic Letters, 2009, vol. 11, # 4, p. 791 - 794
[2] Australian Journal of Chemistry, 1981, vol. 34, # 6, p. 1319 - 1324
13
[ 78238-14-9 ]
[ 180628-74-4 ]
Reference:
[1] Journal of the American Chemical Society, 2005, vol. 127, # 32, p. 11202 - 11203
[2] Synthesis (Germany), 2016, vol. 48, # 19, p. 3263 - 3271
[3] Journal of the American Chemical Society, 1995, vol. 117, # 43, p. 10777 - 10778
[4] Journal of the American Chemical Society, 1996, vol. 118, # 35, p. 8316 - 8328
With sulfuric acid; at 80℃; for 18.0h;Large scale;
In <strong>[78238-14-9]3-hydroxy-5-nitrobenzoic acid</strong> (5.9 kg, 32.2 mol), methanol (60 L) was added, and sulfuric acid (375 ml, catalytic amount) was slowly added thereto, followed by refluxing and stirring at 80 C. for 18 hours. After completing the reaction, the reactant was cooled to room temperature. Purified water (50 L) was added thereto, and methanol was distilled off under a reduced pressure. The solid thus produced was stirred at 10 C. for 1 hour and filtered. The filtrant was washed with purified water, and dried at 60 C. to obtain the title compound (5.52 kg, yield: 87%, yellow solid). 1H-NMR (400 MHz, DMSO-d6) delta 10.91 (s, 1H), 8.04 (s, 1H), 7.74 (s, 1H), 7.66 (s, 1H), 3.88 (s, 3H)
With sulfuric acid; at 20 - 60℃;
Example 240a Methyl 3-hydroxy-5-nitrobenzoate To a clean, dry 100 mL round bottom flask is added <strong>[78238-14-9]3-hydroxy-5-nitrobenzoic acid</strong> (1 g, 5.5 mmole, 1 eq) followed by 10 mL methanol and 2 mL of concentrated sulfuric acid. The exothermic reaction mixture reached 60 C. prior to cooling to room temperature. The reaction mixture was stirred for 18 h prior to partitioning between ethyl acetate and water. After extraction, the organic layer was dried over magnesium sulfate, filtered and evaporated. A white solid product was obtained (1 g, 100%). Calc'd for C8H7NO5; m/z (M+H+)=198; found 198.
3.9 g
With thionyl chloride; at 0 - 6℃; for 3.0h;
o a solution of <strong>[78238-14-9]3-hydroxy-5-nitrobenzoic acid</strong> (3.7 g, 20.00 mmol) in MeOH (70.0 mL), SOCl2(12.0 mL) was added at 0C. The reaction mixture was stirred at 6C for 3 hours, and concentrated under reduced pressure. Water was added to the residue, followed by extracting with EtOAc. The organic extract was washed with brine, dried over anhydrous Na2S04, concentrated under reduced pressure to obtain methyl 3-hydroxy- 5-nitrobenzoate (3.9 g) as an off-white solid without purification.1H-NMR (300MHz, DMSO-d6) delta 10.96 (s, 1H), 8.08 (m, 1H), 7.78 (m, 1H), 7.70 (m, 1H), 3.90 (s, 3H)
With palladium on activated charcoal; hydrogen; In methanol; under 760.051 Torr; for 2h;
Compound 5C was dissolved in methanol (20 mL) and hydrogenated under normal pressure for 2 hours under Pd/C. The diatomaceous earth was filtered to remove Pd/C, and methanol was spun off to obtain a crude product of compound 8D, which was directly taken to the next step.
With boron tribromide; In dichloromethane; at 20℃; for 8h;
<Example 100> Synthesis of 8-[(Dimethylamino)methyl]-10-etoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-5(6H)-one dihydrochloride Step 1: Synthesis of Ethyl 3-etoxy-5-nitrobenzoate [Show Image] 3-Methoxy-5-nitrobenzoic acid (10 g, 50.7 mmol) prepared in step 1 of Example 72 was dissolved in dichloromethane (200 ml), added with 1 M boron tribromide dichloromethane solution. The reaction mixture was stirred at room temperature for 8 hours. The mixture was poured into ice water and washed with dichloromethane. The water layer was concentrated under reduced pressure and dried in vacuo. The residue was dissolved in N,N-dimethylformamide (150 ml), added dropwise with potassium carbonate (42 g, 304 mmol) and iodoethane (20.2 ml, 253 mmol). The mixture was then stirred for one day at 60 C and poured into ice water. The solution was extracted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (hexane : ethyl acetate = 5 : 1) to obtain the title compound (8.49 g, yield:70 % , yellow solid). 1H NMR(400MHz, CDCl3)delta 8.44(s, 1H), 7.90-7.88(m, 2H), 4.43(q, J=3.6Hz, 2H), 4.16(q, J=3.4Hz, 2H) 1.48(t, J=7.2Hz, 3H), 1.43(t, J=7.2Hz, 3H).
3-Methoxy-5-nitrobenzoic acid (10 g, 50.7 mmol) prepared in step 1 of Example 72 was dissolved in dichloromethane (200 ml), added with 1 M boron tribromide dichloromethane solution. The reaction mixture was stirred at room temperature for 8 hours. The mixture was poured into ice water and washed with dichloromethane. The water layer was concentrated under reduced pressure and dried in vacuo. The residue was dissolved in N,N-dimethylformamide (150 ml), added dropwise with potassium carbonate (42 g, 304 mmol) and iodoethane (20.2 ml, 253 mmol). The mixture was then stirred for one day at 60 C. and poured into ice water. The solution was extracted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (hexane:ethyl acetate=5:1) to obtain the title compound (8.49 g, yield: 70%, yellow solid).1H NMR(400 MHz, CDCl3)delta 8.44(s, 1H), 7.90-7.88(m, 2H), 4.43(q, J=3.6 Hz, 2H), 4.16(q, J=3.4 Hz, 2H) 1.48(t, J=7.2 Hz, 3H), 1.43(t, J=7.2 Hz, 3H).
With boron tribromide; In dichloromethane; at -10 - 20℃; for 15h;
Boron tribromide (1.26 mL, 13 mmol) at -10 °CAdd dropwise to compound 5B (860 mg, 4.36 mmol)In a solution of dichloromethane (20 mL), the mixture was reacted at room temperature for 15 hours.After cooling with ice water, add 10 mL of water and continue to stir for 30 minutes.Ethyl acetate extraction (3 × 50 mL), washed with saturated brine.Dry over anhydrous sodium sulfate, filter,Solvent removal gave the crude product of compound 5C directly to the next step.
With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 16.0h;
a) 3-Methoxy-5-nitro-benzoic acid methyl esterTo a solution of 12.82 g (68.6 mmol) <strong>[78238-14-9]3-hydroxy-5-nitrobenzoic acid</strong> in 70 ml DMF are added 28.7 g (206 mmol) powdered potassium carbonate, the mixture is cooled to 0 0C and 9.46 ml (151 mmol) methyl iodide are added. The reaction mixture is allowed to warm to rt and stirring is continued for 16 h. 350 ml water are added and the mixture is extracted with toluene. The combined organic layers are washed with water, dried with sodium sulfate and evaporated to yield the product as yellow solid.1H-NMR (400 MHz, d6-DMSO): 8.19 (dd, 1 H), 7.95 (t, 1 H), 7.81 (q, 1 H), 3.94 (s, 3H), 3.91 (s, 3H).
4-benzyl-3-{3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-3-[3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-5-nitro-phenyl]-2-methyl-propionyl}-oxazolidin-2-one[ No CAS ]
Acetic acid (R)-1-(3-hydroxy-5-{(Z)-4-[(4R,5S,6S)-6-(2-hydroxy-ethyl)-2,2,5-trimethyl-[1,3]dioxan-4-yl]-pent-3-enyl}-phenyl)-3-methoxy-5-oxo-pyrrolidin-2-yl ester[ No CAS ]
((4S,5S,6R)-6-{(Z)-4-[3-(tert-Butyl-dimethyl-silanyloxy)-5-((R)-2-hydroxy-3-methoxy-5-oxo-pyrrolidin-1-yl)-phenyl]-1-methyl-but-1-enyl}-2,2,5-trimethyl-[1,3]dioxan-4-yl)-acetaldehyde[ No CAS ]
Acetic acid (R)-1-(3-hydroxy-5-{(Z)-4-[(4R,5S,6S)-2,2,5-trimethyl-6-(2-oxo-ethyl)-[1,3]dioxan-4-yl]-pent-3-enyl}-phenyl)-3-methoxy-5-oxo-pyrrolidin-2-yl ester[ No CAS ]
Acetic acid (R)-1-(3-(tert-butyl-dimethyl-silanyloxy)-5-{(Z)-4-[(4R,5S,6S)-2,2,5-trimethyl-6-(2-oxo-ethyl)-[1,3]dioxan-4-yl]-pent-3-enyl}-phenyl)-3-methoxy-5-oxo-pyrrolidin-2-yl ester[ No CAS ]
(R)-1-[3-((Z)-4-{(4R,5S,6S)-6-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-2,2,5-trimethyl-[1,3]dioxan-4-yl}-pent-3-enyl)-5-(tert-butyl-diphenyl-silanyloxy)-phenyl]-5-hydroxy-4-methoxy-pyrrolidin-2-one[ No CAS ]
Acetic acid (R)-1-[3-((Z)-4-{(4R,5S,6S)-6-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2,2,5-trimethyl-[1,3]dioxan-4-yl}-pent-3-enyl)-5-(tert-butyl-diphenyl-silanyloxy)-phenyl]-3-methoxy-5-oxo-pyrrolidin-2-yl ester[ No CAS ]
(R)-1-[3-((Z)-1-Benzenesulfonyl-4-{(4R,5S,6S)-6-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2,2,5-trimethyl-[1,3]dioxan-4-yl}-pent-3-enyl)-5-(tert-butyl-diphenyl-silanyloxy)-phenyl]-5-hydroxy-4-methoxy-pyrrolidin-2-one[ No CAS ]
(R)-N-[3-((Z)-1-Benzenesulfonyl-4-{(4R,5S,6S)-6-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2,2,5-trimethyl-[1,3]dioxan-4-yl}-pent-3-enyl)-5-(tert-butyl-diphenyl-silanyloxy)-phenyl]-4-(tert-butyl-dimethyl-silanyloxy)-3-methoxy-butyramide[ No CAS ]
3-allyloxy-5-nitro-benzoic acid allyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
In water; N,N-dimethyl-formamide;
Allyl 3-allyloxy-5-aminobenzoate <strong>[78238-14-9]3-Hydroxy-5-nitrobenzoic acid</strong> (3.9 g, 21.3 mM) was dissolved in DMF (55 ml), and anhydrous K2 CO3 (11.78 g, 76.5 mM) added with stirring. Allyl bromide (5.4 ml, 62.4 mM) was run in, and the mixture stirred for 18 hours at ambient temperature. The solvent was removed by evaporation, the residue treated with water, the pH was adjusted to 5.5, and product was extracted into ethyl acetate. The combined extracts were washed with aqueous NaH2 PO4, water, brine, and dried over MgSO4. The residue after evaporation was subjected to chromatography on silica, eluding with a mixture of petrol/EtOAc (10:1), to give allyl 3-allyloxy-5-nitrobenzoate (5.94 g, 90%). Nmr (CDCl3): delta4.66 (dt, 2H); 4.87 (dt, 2H); 5.31-5.52 (m, 4H); 5.94-6.14 (m, 2H); 7.92 (m, 2H); 8.46 (t, 1H).
3-allyloxy-5-nitro-benzoic acid allyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; potassium iodide; In acetone; for 40.0h;Heating / reflux;
3-Nitro-5-hydroxy-benzoic acid (500 mg, 2.73 mmol, 1 eq) is dissolved in acetone (7 ml). Potassium carbonate (877 mg, 6.28 mmol, 2.3 eq), allyl bromide (1.21 ml, 13.92 mmol, 5.1 eq) and potassium iodide (907 mg, 5.46 mmol, 2 eq) are added to the reaction mixture. The reaction mixture is heated for 40 h at reflux temperature and then diluted with water and EtOAc. The organic layer is separated, washed with brine, dried over sodium sulfate, filtered and concentrated. The product is purified by chromatography on silica (EtOAc/hexane 1/9). MS(ES+): 281 [M+NH4fHPLC (Nucleosil C18HD, 4x70 mm, 3 mum, 20-100% MeCN (6 min), 100% MeCN (1.5 min)) retention time = 5.85 min
3-Hydroxy-5-nitrobenzoic acid (8): Five (5) g (23.6 mmol) 7 were dissolved in 56 mL acetic acid by heating to light reflux under nitrogen atmosphere and 82 mL aqueous hydrobromic acid (48%) were added. The yellow solution was kept under reflux for 16 h. After the reaction mixture had been concentrated, the remaining orange solid was taken up in ethyl acetate, washed with water, and brine, dried with MgSO4 and concentrated again. To remove acetic acid, it was suspended in heptane and rotovapped several times. The orange solid could be recrystallized from 2 N HCl, affording 3.25 g (75%) of a yellow crystalline solid. As alternative solvent system for crystallization, ethyl acetate/hexanes can be used. The reaction can be followed by TLC: MeOH/ethyl; acetate 1:1, Rf (product)=0.73. mp 194-195 C. 2; 1H NMR (acetone-d6) delta8.39-8.25 (m, 1H), 7.89-7.84 (m, 2H).
(1) A method for specifically cleaving a Calpha-C bond of a peptide backbone and/or a side chain bond of a protein or a peptide, comprising irradiating a protein or a peptide with laser light in the presence of at least one hydroxynitrobenzoic acid selected from the group consisting of:3-hydroxy-2-nitrobenzoic acid:4-hydroxy-3-nitrobenzoic acid:5-hydroxy-2-nitrobenzoic acid:3-hydroxy-5-nitrobenzoic acid:4-hydroxy-2-nitrobenzoic acid:
irradiating a protein or a peptide with laser light in the presence of at least one hydroxynitrobenzoic acid selected from the group consisting of:3-hydroxy-2-nitrobenzoic acid:4-hydroxy-3-nitrobenzoic acid:5-hydroxy-2-nitrobenzoic acid:3-hydroxy-5-nitrobenzoic acid:4-hydroxy-2-nitrobenzoic acid:
is an ISD ion theoretical value list of Amyloid beta [1-40].shows stereoscopic microphotographs each showing an example of condition of a residue after dropping, on a sample plate, a peptide sample solution of Amyloid beta [1-40] and a matrix solution using:(A) 3-hydroxy-2-nitrobenzoic acid (3H2NBA), (B) 4-hydroxy-3-nitrobenzoic acid (4H3NBA), (C) 5-hydroxy-2-nitrobenzoic acid (5H2NBA), (D) 3-hydroxy-5-nitrobenzoic acid (3H5NBA), (E) 4-hydroxy-2-nitrobenzoic acid (4H2NBA), (F) 5-nitrosalicylic acid (5-NSA), or (G) 1,5-diaminonaphthalene (1,5-DAN)
72
[ 78238-14-9 ]
[ 100-39-0 ]
[ 661478-70-2 ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In N,N-dimethyl-formamide;
Benzyl 3-benzyloxy-5-nitrobenzoate (12): Compound 12 was prepared from <strong>[78238-14-9]3-hydroxy-5-nitrobenzoic acid</strong> (8), following the same protocol as for the synthesis of iso-pentyl 3-iso-pentyloxy-5-nitrobenzoate (9). Scale: 2 g (10.9 mmol) 8; 5.2 mL (43.6 mmol) benzyl bromide; 6.03 g (43.6 mmol) K2CO3; 15 mL DMF anhydrous. Crude yield: 6.5 g dark red oil. Column chromatography (hexanes/ethyl acetate, 9:1, Rf=0.5), purified yield: 2.58 g white solid (65%). 1H NMR (CDCl3) delta8.49 (dd, J1=1.4 Hz, J2=2.0 Hz, 1H), 8.01-7.98 (m, 2H), 7.49-7.34 (m, 10H), 5.41 (s, 2H, PhCH2), 5.19 (s, 2H, PhCH2).
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 24.0h;
<Example 100> Synthesis of 8-[(Dimethylamino)methyl]-10-etoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-5(6H)-one dihydrochloride Step 1: Synthesis of Ethyl 3-etoxy-5-nitrobenzoate [Show Image] 3-Methoxy-5-nitrobenzoic acid (10 g, 50.7 mmol) prepared in step 1 of Example 72 was dissolved in dichloromethane (200 ml), added with 1 M boron tribromide dichloromethane solution. The reaction mixture was stirred at room temperature for 8 hours. The mixture was poured into ice water and washed with dichloromethane. The water layer was concentrated under reduced pressure and dried in vacuo. The residue was dissolved in N,N-dimethylformamide (150 ml), added dropwise with potassium carbonate (42 g, 304 mmol) and iodoethane (20.2 ml, 253 mmol). The mixture was then stirred for one day at 60 C and poured into ice water. The solution was extracted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (hexane : ethyl acetate = 5 : 1) to obtain the title compound (8.49 g, yield:70 % , yellow solid). 1H NMR(400MHz, CDCl3)delta 8.44(s, 1H), 7.90-7.88(m, 2H), 4.43(q, J=3.6Hz, 2H), 4.16(q, J=3.4Hz, 2H) 1.48(t, J=7.2Hz, 3H), 1.43(t, J=7.2Hz, 3H).
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 24.0h;
3-Methoxy-5-nitrobenzoic acid (10 g, 50.7 mmol) prepared in step 1 of Example 72 was dissolved in dichloromethane (200 ml), added with 1 M boron tribromide dichloromethane solution. The reaction mixture was stirred at room temperature for 8 hours. The mixture was poured into ice water and washed with dichloromethane. The water layer was concentrated under reduced pressure and dried in vacuo. The residue was dissolved in N,N-dimethylformamide (150 ml), added dropwise with potassium carbonate (42 g, 304 mmol) and iodoethane (20.2 ml, 253 mmol). The mixture was then stirred for one day at 60 C. and poured into ice water. The solution was extracted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (hexane:ethyl acetate=5:1) to obtain the title compound (8.49 g, yield: 70%, yellow solid).1H NMR(400 MHz, CDCl3)delta 8.44(s, 1H), 7.90-7.88(m, 2H), 4.43(q, J=3.6 Hz, 2H), 4.16(q, J=3.4 Hz, 2H) 1.48(t, J=7.2 Hz, 3H), 1.43(t, J=7.2 Hz, 3H).