* 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.
Reference：
[1] Synthetic Communications, 1991, vol. 21, # 7, p. 959 - 964
[2] Journal of Medicinal Chemistry, 1990, vol. 33, # 9, p. 2621 - 2629
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 3, p. 403 - 427
4
[ 2365-48-2 ]
[ 6361-21-3 ]
[ 20699-86-9 ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;
To a solution of 2-Chloro-5-nitrobenzaIdehyde (3.7 g, 0.020 mol) in N, N- Dimethylformamide (40 ml_) was added methyl thioglyocolate (1.82 ml_, 0.020 mol) followed by K2CO3 (3.3 g, 0.024 mol). The reaction mixture was stirred at rt overnight. Then, water was added to the reaction mixture and the suspension was filtered. The residue was subsequently washed with water to yield the product 6-Nitro- benzo[b]thiophene-2-carboxylic acid methyl ester as yellow solid. Yield: 95 percent.
94%
With potassium carbonate In water; N,N-dimethyl-formamide at 20℃;
Potassium carbonate (1.73 g, 12.5 mmol) was added to a solution of 2-chloro-5-nitrobenzaldehyde (1.94 g, 10.5 mmol) and methyl 2-mercapto acetate (1.11 g, 10.5 mmol) in DMF (21 mL), and the mixture was stirred at room temperature overnight. Water (100 mL) was added thereto, then the reaction solution was stirred at room temperature for 1 hour, and then the obtained precipitate was filtered out and dried to obtain the title compound (2.35 g, 94percent). 1H-NMR (d-DMSO): δ 9.00 (s, 1H), 8.47-8.42 (m, 1H), 8.40-8.28 (m, 2H), 3.92 (s, 3H).
66%
Stage #1: With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667 h; Stage #2: at 20 - 100℃; for 6 h;
Methyl thioglycolate (19.62 mL, 0.216 mol) was added dropwise, via syringe pump, to a stirred suspension of 95percent sodium hydride (5.99 g, 0.237 mol) in dry N,N-dimethyl- formamide (400 mL) at r.t. under nitrogen (CAUTION : hydrogen evolution). Upon complete addition, the reaction was stirred for 10 min and then a solution of 2-chloro-5- nitrobenzaldehyde (40.0 g, 0.216 mol) in DMF (120 mL) was added. The solution turned orange and a gentle exotherm was observed. After Ih, the now yellow mixture was heated to 100 °C for 5 h. The mixture turned amber in appearance. After cooling to r.t. the mixture was poured into 1 N aqueous hydrochloric acid (500 mL). The resulting yellow precipitate was filtered off and washed with water (250 mL). The solid was suspended in hot methanol / ethyl acetate (1:1) (1000 mL) and allowed to cool to r.t. The EPO <DP n="28"/>resulting solid was filtered off and air dried to yield methyl 5-nitrobenzo[b]thiophene-2- carboxylate (33.77 g, 66percent) as a tan amorphous solid. 1H NMR δ Cd6-DMSO, 400 MHz) 3.92 (s, 3 H), 8.32 (dd, / = 9, 2 Hz, 1 H), 8.37 (d, / = 9 Hz, 1 H), 8.45 (s, 1 H), 9.00 (d, / = 2 Hz, 1 H).
95%
With sodium methylate In methanol
Preparation of Methyl 5-Nitrobenzo[b]thiophene-2-Carboxylate A 2000 ml 3-necked round-bottomed flask, 250 ml pressure equalized dropping funnel, Teflon stirrer, and gas inlet were oven-dried for 12 hours at 160° C. The apparatus was rapidly assembled, fitted with a thermometer, flushed with dry nitrogen gas, and allowed to cool to room temperature. The cooled flask was charged with methanol (600 ml) and methyl thioglycolate (28.6 g, 0.27 mole). Sodium methoxide (19,98 g, 0.37 mole) in methanol (125 ml) was added to the reaction mixture over 10 minutes while stirring. The reaction mixture was then warmed to 40° C. and a solution of 2-chloro-5-nitrobenzaldehyde (28.6 g, 0.27 mole) in methanol (300 ml) was added over a period of about 20 minutes. The resulting slurry was stirred at 40° C. for 1 hour, cooled to room temperature, and acidified with 2M hydrochloric acid. The resulting white solid was filtered, washed with water (2*300 ml) and air-dried to give 61 g (95percent) of methyl 5-nitrobenzothiophene-2-carboxylate. See, R. A. Zambias, M. L. Hammond, Synthetic Communications, 21:959 (1991).
Reference：
[1] Synthetic Communications, 1991, vol. 21, # 7, p. 959 - 964
[2] Organic and Biomolecular Chemistry, 2015, vol. 13, # 24, p. 6814 - 6824
[3] Patent: WO2006/101454, 2006, A1, . Location in patent: Page/Page column 45
[4] Patent: EP2876105, 2015, A1, . Location in patent: Paragraph 0945; 0946
[5] Heterocycles, 2008, vol. 75, # 8, p. 1913 - 1929
[6] Journal of the American Chemical Society, 2000, vol. 122, # 27, p. 6382 - 6394
[7] Patent: WO2006/66172, 2006, A1, . Location in patent: Page/Page column 26-27
[8] Journal of Medicinal Chemistry, 1990, vol. 33, # 9, p. 2621 - 2629
[9] Patent: US5863936, 1999, A,
[10] Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7108 - 7118
[11] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 3, p. 403 - 427
5
[ 96-35-5 ]
[ 6361-21-3 ]
[ 20699-86-9 ]
Yield
Reaction Conditions
Operation in experiment
69%
With potassium carbonate In N,N-dimethyl-formamide
Step 1: Methyl-5-nitro-benzo[b]thiophene-2-carboxylate (584) A stirring suspension of 5-nitro-2-chloro-benzaldehyde (4.0 g, 21.6 mmol) in DMF (40 ml) at 5° C. was treated with K2CO3(3.52 g, 25.5 mmol) followed by methylglycolate (1.93 ml, 21.6 mmol). The resulting solution was warmed to 25° C. and stirred for 20 h. The solution was then poured into 250 ml of ice H2O and the white precipitate that formed was collected by filtration. Crystallization from EtOAc afforded fine pale orange needles of 584 (3.54 g, 69percent). LRMS: 237.0 (Calc.); 238.1 (found). 1H NMR: (DMSO) δ (ppm): 9.00 (d, J=2.2 Hz, 1H), 8.45 (s, 1H), 8.39-8.30 (m, 2H), 3.93 (s, 3H).
69%
With potassium carbonate In N,N-dimethyl-formamide
Step 1: Methyl-5-nitro-benzo[b]thiophene-2-carboxylate (584) A stirring suspension of 5-nitro-2-chloro-benzaldehyde (4.0 g, 21.6 mmol) in DMF (40 ml) at 5° C. was treated with K2CO3(3.52 g, 25.5 mmol) followed by methylglycolate (1.93 ml, 21.6 mmol). The resulting solution was warmed to 25° C. and stirred for 20h. The solution was then poured into 250 ml of ice H2O and the white precipitate that formed was collected by filtration. Crystallization from EtOAc afforded fine pale orange needles of 584 (3.54 g, 69percent). LRMS: 237.0 (Calc.); 238.1 (found). 1H NMR: (DMSO) δ (ppm): 9.00 (d, J=2.2 Hz, 1H), 8.45 (s, 1H), 8.39-8.30 (m, 2H), 3.93 (s, 3H).
69%
With potassium carbonate In N,N-dimethyl-formamide
Step 1: Methyl-5-nitro-benzo[b]thiophene-2-carboxylate (584) A stirring suspension of 5-nitro-2-chlorobenzaldehyde (4.0 g, 21.6 mmol) in DMF (40 ml) at 5° C. was treated with K2CO3(3.52 g, 25.5 mmol) followed by methylglycolate (1.93 ml, 21.6 mmol). The resulting solution was warmed to 25° C. and stirred for 20 h. The solution was then poured into 250 ml of ice H2O and the white precipitate that formed was collected by filtration. Crystallization from EtOAc afforded fine pale orange needles of 584 (3.54 g, 69percent). LRMS: 237.0 (Calc.). 238.1 (found). 1H NMR: (DMSO) δ (ppm): 9.00 (d, J=2.2 Hz, 1H), 8.45 (s, 1H), 8.39-8.30 (m, 2H), 3.93 (s, 3H).
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 2 h;
A mixture of 5.00 g of 2-fluoro-5-nitrobenzaldehyde, 3.76 g of methyl thioglycolate, 4.18 g of potassium carbonate,and 30 ml of N,N-dimethylformamide was stirred for 2 hours at 60°C. The reaction mixture was cooled to roomtemperature. Water was added to the reaction mixture, and extraction was performed three times by using ethyl acetate.The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and thenconcentrated under reduced pressure. The residues were recrystallized from methanol, thereby obtaining 5.8 g of methyl5-nitrobenzo[b]thiophene-2-carboxylate
With hydrogenchloride; tin(ll) chloride In water at 80℃; for 1 h;
To the above product 6-Nitro-benzo[b]thiophene-2-carboxylic acid methyl ester (1 g, 0.004 mol) and SnCI2-H2O (4.85 g, 0.017 mol) was added concentrated HCI (20 ml_, 0.24 mol). The reaction was stirred at 80 0C for 1 hour, then cooled to low temperature. Then, the pH of the reaction mixture was raised to pH = 9 ~ 11 using 10percent NaOH solution in water. The suspension was then filtered and residue was washed with H2O followed by CH3OH to yield the product as yellow solid quantitatively.
83%
With hydrogen In methanol for 2 h;
Synthesis of Benzofuran and Benzo [b] thiophene Derivatives; Synthesis of 5- (3-chloro-2-methvl-benzenesulfonylamino) -benzorblthiophene-2-carboxylic acid methyl ester, STX 971 (KRB01096) :; 5-amino-benzo [b] thiophene-2-carboxylic acid methyl ester (KRB01094) :; To a solution of 5-nitro-benzo [b] thiophene-2-carboxylic acid methyl ester [15] (130 mg, 0.548 mmol) in methanol (30 mL) was added 5percent palladium on carbon (20 mg) and the mixture was stirred under 1 atm Ha for 2 h. The mixture was filtered through celite and the filtrate evaporated. The residue was passed through a silica column to afford 5-amino- benzo [b] thiophene-2-carboxylic acid methyl ester as a pale yellow solid (94 mg, 83percent), single spot at Rf 0.75 (95: 5 dichloromethane : methanol).'H NMR (CDCl3) : No. 7.86 (1H, s), 7.61 (1H, d, J=8. 7 Hz), 7.11 (1H, d, J=2. 2 Hz), 6.88 (1H, dd, J=8.7, 2. 5 Hz), 3.91 (3H, s), 3.76 (2H, s, N-H2) [16].
Reference：
[1] Patent: WO2006/101454, 2006, A1, . Location in patent: Page/Page column 45
[2] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 5, p. 1611 - 1618
[3] Journal of the American Chemical Society, 2000, vol. 122, # 27, p. 6382 - 6394
[4] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 9, p. 963 - 967
[5] Patent: WO2005/42513, 2005, A1, . Location in patent: Page/Page column 57-58
[6] Patent: US2004/142953, 2004, A1,
[7] Patent: US2005/288282, 2005, A1,
[8] Patent: US6897220, 2005, B2,
[9] Patent: EP2926660, 2015, A1, . Location in patent: Paragraph 0384
With potassium hydroxide; In water; for 3.0h;Reflux;
General procedure: The solution of compound 2a-2n (1.1 mmol) in water (10 mL)was stirred and then potassium hydroxide pellets (5.4 mmol) wereadded, which was refluxed for 3 h. The aqueous layer was thenacidified to pH 1 with 1M hydrochloric acid solution. The aqueouslayer was extracted with dichloromethane (3 x 15 mL). The combinedorganic layers were dried with sodium sulfate, filtered, andthe solvents were removed under reduced pressure to afford thetitle compound 3a-3n [31,34].
360 mg
With lithium hydroxide monohydrate; In methanol; water; at 75℃; for 1.0h;
A mixture of 400 mg of methyl 5-nitrobenzo[b]thiophene-2-carboxylate, 85 mg of lithium hydroxide monohydrate,5 ml of water, and 15 ml of methanol was stirred for 1 hour at 75C. After being cooled to room temperature, the reactionmixture was concentrated under reduced pressure. Water was added to the residues, and the residue was washed threetimes with tert-butyl methyl ether. Concentrated hydrochloric acid water added to the aqueous layer, and then extractionwas performed three times by using tert-butyl methyl ether. The collected organic layer was washed with saturatedsaline, dried over magnesium sulfate, and then concentrated under reduced pressure, thereby obtaining 360 mg of 5-nitrobenzo[b]thiophene-2-carboxylic acid (hereinafter, described as a "compound 18 of the present invention").1H-NMR (DMSO-D6) delta: 13.88 (br s, 1H), 8.99 (d, 1H, J = 2.2 Hz), 8.36 (s, 1H), 8.35 (d, 1H, J = 9.3 Hz), 8.30 (dd, 1H, J= 2.2, 9.3 Hz).
880 mg
With water; sodium hydroxide; at 0℃; for 2.0h;Reflux; Inert atmosphere;
To a solution of methyl thioglycolate (530 mg, 5 mmol) in absolutemethanol (20 mL) at 40 C was added a solution of sodiummethoxide (320 mg, 6 mmol) in methanol (5 mL). The reactionmixture was heated to 50 C and treated drop wise a solution of2-chloro-5-nitro benzaldehyde (49) (1 g, 5 mmol) in methanol(10 mL) was added drop wise. A precipitate was formed duringthe addition. The resulting suspension was heated at 60 C for1.5 h and cooled to RT. A solution of sodium hydroxide (2 mL,2.5 N solution) was added and the reaction mixture was refluxedfor 2 h, cooled to 0 C and acidified with conc. hydrochloric acid(pH 4). The resulting solid was isolated by filtration, redissolvedin hot sodium hydroxide solution, and acidified with drop wiseaddition of conc. hydrochloric acid. The solid obtained was isolatedby filtration, washed with water, co-evaporated with toluene, anddried to get 880 mg 5-nitrobenzothiophene-2-carboxylic acid (50)(74%).1H NMR (DMSO, 400 MHz): 8.90 (d, 1H), 8.75 (d, 1H), 8.32 (t,1H), 8.05 (d, 1H), 3.33 (s, 3H). MS (electrospray): m/z = 222 [M-1].
With hydrogenchloride; tin(ll) chloride; In water; at 80℃; for 1h;
To the above product 6-Nitro-benzo[b]thiophene-2-carboxylic acid methyl ester (1 g, 0.004 mol) and SnCI2-H2O (4.85 g, 0.017 mol) was added concentrated HCI (20 ml_, 0.24 mol). The reaction was stirred at 80 0C for 1 hour, then cooled to low temperature. Then, the pH of the reaction mixture was raised to pH = 9 ~ 11 using 10% NaOH solution in water. The suspension was then filtered and residue was washed with H2O followed by CH3OH to yield the product as yellow solid quantitatively.
83%
With hydrogen;5%-palladium/activated carbon; In methanol; under 760.051 Torr; for 2h;
Synthesis of Benzofuran and Benzo [b] thiophene Derivatives; Synthesis of 5- (3-chloro-2-methvl-benzenesulfonylamino) -benzorblthiophene-2-carboxylic acid methyl ester, STX 971 (KRB01096) :; 5-amino-benzo [b] thiophene-2-carboxylic acid methyl ester (KRB01094) :; To a solution of 5-nitro-benzo [b] thiophene-2-carboxylic acid methyl ester [15] (130 mg, 0.548 mmol) in methanol (30 mL) was added 5% palladium on carbon (20 mg) and the mixture was stirred under 1 atm Ha for 2 h. The mixture was filtered through celite and the filtrate evaporated. The residue was passed through a silica column to afford 5-amino- benzo [b] thiophene-2-carboxylic acid methyl ester as a pale yellow solid (94 mg, 83%), single spot at Rf 0.75 (95: 5 dichloromethane : methanol).'H NMR (CDCl3) : No. 7.86 (1H, s), 7.61 (1H, d, J=8. 7 Hz), 7.11 (1H, d, J=2. 2 Hz), 6.88 (1H, dd, J=8.7, 2. 5 Hz), 3.91 (3H, s), 3.76 (2H, s, N-H2) [16].
With hydrogenchloride; In methanol; ethyl acetate;
Step 2: Methyl-5-amino-benzo[b]thiophene-2-carboxylate (588) A suspension of 584 (3.52 g, 14.8 mmol) in methanol (100 ml) was treated with Fe powder (6.63 g, 118.7 mmol). The resulting suspension was heated to reflux, and 12M HCl (8.5 ml) was slowly added over 15 min. The resulting green dark suspension was refluxed for an additional 3 h, then cooled and concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3, then brine, dried over MgSO4, filtered and concentrated to afford (2.57 g, 84%). 1H NMR: (DMSO) delta (ppm): 7.92 (s, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.05 (d, J=1.5 Hz, 1H), 6.88 (dd, J=1.8, 8.4 Hz, 1H), 5.27 (s, 2H), 3.85 (s, 3H). LRMS: 207.0 (Calc.); 208.1 (found).
With hydrogenchloride; In methanol; ethyl acetate;
Step 2: Methyl-5-amino-benzo[b]thiophene-2-carboxylate (588) A suspension of 584 (3.52 g, 14.8 mmol) in methanol (100 ml) was treated with Fe powder (6.63 g, 118.7 mmol). The resulting suspension was heated to reflux, and 12M HCl (8.5 ml) was slowly added over 15 min. The resulting green dark suspension was refluxed for an additional 3 h, then cooled and concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3, then brine, dried over MgSO4, filtered and concentrated to afford (2.57 g, 84%). 1H NMR: (DMSO) delta (ppm): 7.92 (s, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.05 (d, J=1.5 H, 1H), 6.88 (dd, J=1.8, 8.4 Hz, 1H), 5.27 (s, 2H), 3.85 (s, 3H). LRMS: 207.0 (Calc.); 208.1 (found).
With hydrogenchloride; In methanol; ethyl acetate;
Step 2: Methyl-5-amino-benzo[b]thiophene-2-carboxylate (588) A suspension of 584 (3.52 g, 14.8 mmol) in methanol (100 ml) was treated with Fe powder (6.63 g, 118.7 mmol). The resulting suspension was heated to reflux, and 12M HCl (8.5 ml) was slowly added over 15 min. The resulting green dark suspension was refluxed for an additional 3 h, then cooled and concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3, then brine, dried over MgSO4, filtered and concentrated to afford (2.57 g, 84%). 1H NMR: (DMSO) delta (ppm): 7.92 (s, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.05 (d, J=1.5 Hz, 1H), 6.88 (dd, J=1.8, 8.4 Hz, 1H), 5.27 (s, 2H), 3.85 (s, 3H). LRMS: 207.0 (Calc.). 208.1 (found).
3-[1-methyl-4[1-methyl-4[5-[4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]benzothiophene-2-carboxamido]-pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine hydrochloride[ No CAS ]
5-[(4-<i>tert</i>-butoxycarbonylamino-1-methyl-1<i>H</i>-imidazole-2-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carboxylic acid methyl ester[ No CAS ]
6-(5-<i>tert</i>-butoxycarbonylamino-benzo[<i>b</i>]thiophene-2-carbonyl)-3,6,7,8-tetrahydro-3,6-diaza-<i>as</i>-indacene-2-carboxylic acid methyl ester[ No CAS ]
7-(2-methoxycarbonyl-benzo[<i>b</i>]thiophen-5-ylcarbamoyl)-1,6-dihydro-2<i>H</i>-3,6-diaza-<i>as</i>-indacene-3-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
5-amino-1<i>H</i>-indole-2-carboxylic acid [2-(1-methyl-5-methylcarbamoyl-1<i>H</i>-pyrrol-3-ylcarbamoyl)-benzo[<i>b</i>]thiophen-5-yl]-amide[ No CAS ]
5-amino-1<i>H</i>-indole-2-carboxylic acid [2-(5-dimethylcarbamoyl-1-methyl-1<i>H</i>-pyrrol-3-ylcarbamoyl)-benzo[<i>b</i>]thiophen-5-yl]-amide[ No CAS ]
5-amino-1<i>H</i>-indole-2-carboxylic acid {2-[5-(2-cyano-ethylcarbamoyl)-1-methyl-1<i>H</i>-pyrrol-3-ylcarbamoyl]-benzo[<i>b</i>]thiophen-5-yl}-amide[ No CAS ]
5-amino-1<i>H</i>-indole-2-carboxylic acid {2-[5-(2-carbamimidoyl-ethylcarbamoyl)-1-methyl-1<i>H</i>-pyrrol-3-ylcarbamoyl]-benzo[<i>b</i>]thiophen-5-yl}-amide[ No CAS ]
4-[(5-[5-(4-dimethylamino-butyrylamino)-1<i>H</i>-indole-2-carbonyl]-amino}-benzo[<i>b</i>]thiophene-2-carbonyl)-amino]-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid[ No CAS ]
4-({5-[(5-<i>tert</i>-butoxycarbonylamino-benzo[<i>b</i>]thiophene-2-carbonyl)-amino]-benzofuran-2-carbonyl}-amino)-1-methyl-1<i>H</i>-imidazole-2-carboxylic acid ethyl ester[ No CAS ]
6-(4-[5-(4-dimethylamino-butyrylamino)-benzo[<i>b</i>]thiophene-2-carbonyl]-amino}-thiophene-2-carbonyl)-3,6,7,8-tetrahydro-3,6-diaza-<i>as</i>-indacene-2-carboxylic acid methyl ester[ No CAS ]
4-({5-[(4-amino-thiophene-2-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
4-({4-[(5-amino-benzo[<i>b</i>]thiophene-2-carbonyl)-amino]-1-methyl-1<i>H</i>-pyrrole-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
4-({5-[(2-amino-thiazole-4-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
4-({5-[(4-amino-1-methyl-1<i>H</i>-pyrrole-2-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
4-({5-[(4-amino-1-methyl-1<i>H</i>-imidazole-2-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
4-({5-[(5-amino-benzofuran-2-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
4-({5-[(5-amino-1<i>H</i>-indole-2-carbonyl)-amino]-benzo[<i>b</i>]thiophene-2-carbonyl}-amino)-1-methyl-1<i>H</i>-pyrrole-2-carboxylic acid methyl ester[ No CAS ]
Preparation of Methyl 5-aminobenzo[b]thiophene-2-Carboxylate In a 250 ml round-bottomed flask fitted with a Teflon stirrer and a reflux condenser, methyl 5-nitrobenzo[b]thiophene-2-carboxylate (10 g, 42.18 mmole) was dissolved in ethanol (100 ml). Tin (II) chloride dihydrate (5 equivalents, 47.60 g, 211 mmole) was added in one lot and the resulting slurry was reluxed for 18 hours while being stirred. The reaction mixture was cooled to room temperature, transferred to a 2000 ml Erlenmeyer flask, and carefully quenched with 5% sodium bicarbonate solution (aprroximately 700 ml) until effervescense was no longer detected. The resulting precipitate was filtered off and air-dried. The dried solid was dissolved in hot ethanol (500 ml), and filtered to remove undissolved material. The filtrate was evaporated in vacuo to give 8.564 g (96%) of methyl 5-aminobenzo[b]thiophene-2-carboxylate.
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 15h;
General procedure: To a stirred solution of compound 1a-1n (9.90 mmol) in DMF (20 mL) were added methyl thioglycolate (10.9 mmol) and potassium carbonate (39.6 mmol). The resulting mixture was stirred at 60 C for 15 h. The DMF was removed under reduced pressure,water (50 mL) was added and the mixture was extracted with ethylacetate (2 x 40 mL). The combined organic layers were dried withsodium sulfate, filtered, and the solvents were removed under reduced pressure to afford the title compound 2a-2n [31,34].
5.8 g
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h;
A mixture of 5.00 g of <strong>[27996-87-8]2-fluoro-5-nitrobenzaldehyde</strong>, 3.76 g of methyl thioglycolate, 4.18 g of potassium carbonate,and 30 ml of N,N-dimethylformamide was stirred for 2 hours at 60C. The reaction mixture was cooled to roomtemperature. Water was added to the reaction mixture, and extraction was performed three times by using ethyl acetate.The collected organic layer was washed with water and saturated saline, dried over magnesium sulfate, and thenconcentrated under reduced pressure. The residues were recrystallized from methanol, thereby obtaining 5.8 g of methyl5-nitrobenzo[b]thiophene-2-carboxylate
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