* 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] Journal of Medicinal Chemistry, 2009, vol. 52, # 6, p. 1518 - 1521
[2] Patent: US2008/188450, 2008, A1, . Location in patent: Page/Page column 14
4
[ 535-80-8 ]
[ 34662-36-7 ]
Yield
Reaction Conditions
Operation in experiment
2.65 g
at 0 - 20℃; for 1 h;
Concentrated sulfuric acid (12 mL) was added to concentrated nitric acid (1.6 mL) under ice cooling, and the mixture was stirred at 0 ° C. for 5 min.3-Chlorobenzoic acid (3 g) was added over 5 minutes, the temperature was raised to room temperature and stirred for 1 hour.The reaction solution was added dropwise to ice-cooled water, and the precipitated solid was collected by filtration and washed with water to give 3-chloro-5-nitrobenzoic acid (Compound 0004-1, 2.65 g) as a white solid.
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 16, p. 4557 - 4561
[2] Patent: JP6052673, 2016, B2, . Location in patent: Paragraph 0081
5
[ 13290-74-9 ]
[ 34662-36-7 ]
Reference:
[1] Journal of the American Chemical Society, 1954, vol. 76, p. 6336,6337
6
[ 20352-84-5 ]
[ 34662-36-7 ]
Reference:
[1] Patent: US2008/188450, 2008, A1,
7
[ 49709-31-1 ]
[ 34662-36-7 ]
Reference:
[1] Journal of Organic Chemistry, 1955, vol. 20, p. 1026,1027
8
[ 578-54-1 ]
[ 34662-36-7 ]
Reference:
[1] Journal of Organic Chemistry, 1955, vol. 20, p. 1026,1027
9
[ 6853-29-8 ]
[ 34662-36-7 ]
Reference:
[1] Journal of Organic Chemistry, 1955, vol. 20, p. 1026,1027
10
[ 33098-65-6 ]
[ 34662-36-7 ]
Reference:
[1] Journal of Organic Chemistry, 1955, vol. 20, p. 1026,1027
11
[ 100-00-5 ]
[ 34662-36-7 ]
Reference:
[1] Yakugaku Zasshi, 1950, vol. 70, p. 25,27[2] Chem.Abstr., 1950, p. 4435
[3] Yakugaku Zasshi, 1950, vol. 70, p. 25,27[4] Chem.Abstr., 1950, p. 4435
12
[ 69422-57-7 ]
[ 34662-36-7 ]
Reference:
[1] Yakugaku Zasshi, 1950, vol. 70, p. 25,27[2] Chem.Abstr., 1950, p. 4435
13
[ 34662-36-7 ]
[ 21961-30-8 ]
Yield
Reaction Conditions
Operation in experiment
96%
With hydrogen In ethanol; water at 20℃; for 18 h;
3-Chloro-5-nitro-benzoic acid (1.590g, 7. [9MMOL)] was stirred under a hydrogen atmosphere in ethanol (40mL) with raney-nickel, (aqueous suspension,-0. 4g) at room temperature and pressure for 18 hours. The reaction mixture was then filtered through celite and evaporated to give the title compound (1.300g, 96percent). [OH] NMR [(400MHZ,] [CDCI3)] 6.86 (1H, s), 7.18 [(1H,] s), 7.22 (1H, s). LC/MS t=2.30 mins [[MH-]] 170.
368 mg
With iron; ammonium chloride In water; isopropyl alcohol at 90℃; for 3 h;
Isopropanol (78 mL),Ammonium chloride (0.18 g) and reduced iron (1.07 g) were added to a mixed solution of water (20 mL)After stirring at 90 ° C. for 1 hour,3-Chloro-5-nitrobenzoic acid (Compound 0004-1, 1.1 g) was slowly added and stirred at 90 ° C. for 3 hours.The reaction solution was cooled to room temperature, washed with methanol, and the filtrate was evaporated under reduced pressure to obtain a crude product. Purification by silica gel column chromatography (methanol-chloroform) gave 3-amino-5-chlorobenzoic acid (Compound 0004-2, 368 mg) as a light brown solid.
Reference:
[1] Patent: WO2003/101959, 2003, A1, . Location in patent: Page 225-226
[2] Justus Liebigs Annalen der Chemie, 1884, vol. 222, p. 73[3] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 312
[4] Journal of the American Chemical Society, 1954, vol. 76, p. 6336,6337
[5] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 16, p. 4557 - 4561
[6] Patent: JP6052673, 2016, B2, . Location in patent: Paragraph 0082
14
[ 34662-36-7 ]
[ 79944-62-0 ]
Yield
Reaction Conditions
Operation in experiment
4.22 g
With borane-THF In tetrahydrofuran at 0 - 20℃;
To a stirred solution of 3-chloro-5-nitrobenzoic acid (5.00 g; 24.8 mmol; ABCR GmbH & CO. KG) in THF (48 mL) at 0°C was added a 1M solution of borane-THF complex in THF (99.2 mL; 99.2 mmol). The mixture was allowed to react at RT overnight. Then, MeOH was cautiously added to the stirred mixture while cooling with an ice bath. The batch was diluted with ethyl acetate and washed with aqueous sodium hydroxide solution (IN) and saturated aqueous sodium chloride solution. The organic phase was dried (sodium sulfate), filtered and concentrated. The residue was purified by chromatography hexane / ethyl acetate 50 percent to 100 percent) to give the pure product (4.22 g; 22.5 mmol). NMR (400MHz, CDC13, 300K) δ = 8.13 (m, 2H), 7.71 (s, 1H), 4.81 (m, 2H), 2.00 (br, 1H).
Step 1: methyl 3-chloro-5-nitrobenzoate A solution (0.96 M) OfNaNO2 (7.0 eq.) in water was added to a solution (0.09 M) of 3-amino-5-nitrobenzoic acid in HCl (cone.) at 00C. The reaction mixture was left to warm up to RT over a period of 30 min and then was added to a solution (1.37 M) of CuCl (10.0 eq.) in water. The reaction mixture was stirred at RT for 3 h and then heated to 700C for 30 min. After addition Of Et2O and water, the organic phase was separated and the aqueous phase extracted with Et2O. The combined organic layers were dried and evaporated to give a solid (MS (ES+) m/z 200, 202 (M+H)+), which was dissolved in MeOH. The resulting solution (0.1 M) was treated with SOCl2 (20 eq.) and the reaction mixture was heated at 800C for 16 h. After evaporation of the solvent, the resulting residue was dissolved in EtOAc and aqueous NaHCO3 (saturated solution). The aqueous phase was separated and the organic phase washed with aqueous NaHCO3 (saturated solution) and brine and dried. Evaporation of the solvent afforded (95percent) the title compound as a white solid; MS (ES+) m/z 216, 218 (M+H)+.
With hydrogen;nickel; In ethanol; water; at 20℃; under 760.051 Torr; for 18h;
3-Chloro-5-nitro-benzoic acid (1.590g, 7. [9MMOL)] was stirred under a hydrogen atmosphere in ethanol (40mL) with raney-nickel, (aqueous suspension,-0. 4g) at room temperature and pressure for 18 hours. The reaction mixture was then filtered through celite and evaporated to give the title compound (1.300g, 96%). [OH] NMR [(400MHZ,] [CDCI3)] 6.86 (1H, s), 7.18 [(1H,] s), 7.22 (1H, s). LC/MS t=2.30 mins [[MH-]] 170.
368 mg
With iron; ammonium chloride; In water; isopropyl alcohol; at 90℃; for 3h;
Isopropanol (78 mL),Ammonium chloride (0.18 g) and reduced iron (1.07 g) were added to a mixed solution of water (20 mL)After stirring at 90 C. for 1 hour,3-Chloro-5-nitrobenzoic acid (Compound 0004-1, 1.1 g) was slowly added and stirred at 90 C. for 3 hours.The reaction solution was cooled to room temperature, washed with methanol, and the filtrate was evaporated under reduced pressure to obtain a crude product. Purification by silica gel column chromatography (methanol-chloroform) gave 3-amino-5-chlorobenzoic acid (Compound 0004-2, 368 mg) as a light brown solid.
With thionyl chloride; N,N-dimethyl-formamide; at 110℃; for 2h;
Example 1) Synthesis of 7V-(3-chloro-5-(2-(3-ethoxy-5- (trifluoromethoxy)phenyl)propan-2-yl)phenyI)-5-(2-(methylsulfonyI)propan-2- yl)benzo [b] thiophene-2-carboxamide (a) Synthesis of 3 -chloro-5-nitrobenzoyl chloride 3-Chloro-5-nitrobenzoic acid (5.0 g, 24.81 mmol) was dissolved in SOCl2 (10.0 mL, 137.00 mmol), and a catalytic amount of anhydrous DMF was added. The reaction mixture was refluxed at 110C for 2 hours and concentrated under reduced pressure to obtain 3-chloro-5-nitrobenzoyl chloride (5.3 g, quant.) as a yellow liquid without purification.
Step 1: methyl 3-chloro-5-nitrobenzoate A solution (0.96 M) OfNaNO2 (7.0 eq.) in water was added to a solution (0.09 M) of 3-amino-5-nitrobenzoic acid in HCl (cone.) at 00C. The reaction mixture was left to warm up to RT over a period of 30 min and then was added to a solution (1.37 M) of CuCl (10.0 eq.) in water. The reaction mixture was stirred at RT for 3 h and then heated to 700C for 30 min. After addition Of Et2O and water, the organic phase was separated and the aqueous phase extracted with Et2O. The combined organic layers were dried and evaporated to give a solid (MS (ES+) m/z 200, 202 (M+H)+), which was dissolved in MeOH. The resulting solution (0.1 M) was treated with SOCl2 (20 eq.) and the reaction mixture was heated at 800C for 16 h. After evaporation of the solvent, the resulting residue was dissolved in EtOAc and aqueous NaHCO3 (saturated solution). The aqueous phase was separated and the organic phase washed with aqueous NaHCO3 (saturated solution) and brine and dried. Evaporation of the solvent afforded (95%) the title compound as a white solid; MS (ES+) m/z 216, 218 (M+H)+.
With thionyl chloride; at 70℃; for 12h;
To a solution of compound 1 (1 g, 5.0 mmol, 1 eq) in 20 mL of methanol was added SOCb (1.2 g, 9.9 mmol, 720 pL, 2 eq) at 25C. The mixture was stirred at 70C for 12 hours. After reaction, it was concentrated under reduced pressure to give a residue, which was diluted with 50 mL of sa/.NaHCCL and extracted with 90 mL of ethyl acetate. The organic phase was separated, dried over anhydrous Na2SC>4, filtered and the filtrate was concentrated under reduced pressure to give 1.1 g of crude compound 2 as a brown solid.
With hydrogenchloride; sodium nitrite;copper(l) chloride; In water; at 20 - 70℃; for 3.5h;
Step 1: methyl 3-chloro-5-nitrobenzoate A solution (0.96 M) OfNaNO2 (7.0 eq.) in water was added to a solution (0.09 M) of 3-amino-5-nitrobenzoic acid in HCl (cone.) at 00C. The reaction mixture was left to warm up to RT over a period of 30 min and then was added to a solution (1.37 M) of CuCl (10.0 eq.) in water. The reaction mixture was stirred at RT for 3 h and then heated to 700C for 30 min. After addition Of Et2O and water, the organic phase was separated and the aqueous phase extracted with Et2O. The combined organic layers were dried and evaporated to give a solid (MS (ES+) m/z 200, 202 (M+H)+), which was dissolved in MeOH. The resulting solution (0.1 M) was treated with SOCl2 (20 eq.) and the reaction mixture was heated at 800C for 16 h. After evaporation of the solvent, the resulting residue was dissolved in EtOAc and aqueous NaHCO3 (saturated solution). The aqueous phase was separated and the organic phase washed with aqueous NaHCO3 (saturated solution) and brine and dried. Evaporation of the solvent afforded (95%) the title compound as a white solid; MS (ES+) m/z 216, 218 (M+H)+.
3-amino-5-chlorobenzoic acid hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; water; under 1551.49 Torr; for 0.5h;
A mixture of <strong>[34662-36-7]3-chloro-5-nitrobenzoic acid</strong> (10.0 g) and 10% Pd/C (0.3 g) in MeOH (100 mL) and 6N HCl (30 mL) was shaken under 30 psi H2 in a Parr apparatus for 30 min, then filtered through Celite and evaporated. The residue was crystallized from 6N HCl to yield the product. More highly purified material was obtained by a second crystallization from water. 1H-NMR (d4-CD3OD): delta 7.24 (1H, dd, J=1.4, 2.0 Hz), 7.20 (1H, dd, J=1.6, 2.0 Hz), 6.87 (1H, t, J=2.0 Hz). 13C-NMR (d4-CD3OD): delta 167.6, 149.5, 134.3, 132.7, 117.8, 117.4, 113.9.
3-Chloro-5-nitrobenzonitrile (30.0 g) was dissolved in a mixture of water (85 mL) and H2SO4 (250 mL) and heated under an N2 atmosphere at 150 C. for 2 h. The mixture was cooled to ambient temperature and poured onto ice (1 L). The resulting solid was collected by vacuum filtration, and the filtrate was extracted with ethyl acetate. The extract and solid were combined, washed with water and brine, then were dried over MgSO4, filtered, and evaporated. The residue was dissolved in 1:1 water/MeOH (200 mL) with heating, treated with decolorizing charcoal and filtered. Water (100 mL) was added and the mixture was allowed to cool and crystallize. The product was obtained as pale yellow crystals. 1H-NMR (d6-DMSO): delta 14.00 (1H, br s), 8.51 (2H, m), 8.29 (1H, m). 13C-NMR (d6-DMSO): delta 164.9, 149.2, 135.2, 135.0, 134.5, 127.7, 122.9.
With sulfuric acid; nitric acid; at 0 - 20℃; for 1h;
Concentrated sulfuric acid (12 mL) was added to concentrated nitric acid (1.6 mL) under ice cooling, and the mixture was stirred at 0 C. for 5 min.3-Chlorobenzoic acid (3 g) was added over 5 minutes, the temperature was raised to room temperature and stirred for 1 hour.The reaction solution was added dropwise to ice-cooled water, and the precipitated solid was collected by filtration and washed with water to give 3-chloro-5-nitrobenzoic acid (Compound 0004-1, 2.65 g) as a white solid.
To a stirred solution of 3-chloro-5-nitrobenzoic acid (5.00 g; 24.8 mmol; ABCR GmbH & CO. KG) in THF (48 mL) at 0C was added a 1M solution of borane-THF complex in THF (99.2 mL; 99.2 mmol). The mixture was allowed to react at RT overnight. Then, MeOH was cautiously added to the stirred mixture while cooling with an ice bath. The batch was diluted with ethyl acetate and washed with aqueous sodium hydroxide solution (IN) and saturated aqueous sodium chloride solution. The organic phase was dried (sodium sulfate), filtered and concentrated. The residue was purified by chromatography hexane / ethyl acetate 50 % to 100 %) to give the pure product (4.22 g; 22.5 mmol). NMR (400MHz, CDC13, 300K) delta = 8.13 (m, 2H), 7.71 (s, 1H), 4.81 (m, 2H), 2.00 (br, 1H).
General procedure: A solution of 2-hydroxybenzohydrazide (1) (0.01 mol) in phosphorous oxychloride (8 ml) and different substituted aromatic acids (0.01 mol) were refluxed for about 18-28 hr in an oil bath. The reaction mixture was cooled to room temperature and poured into crushed ice. On neutralization with 20% NaHCO3 solution, a solid mass separated out, which was filtered, washed with water and recrystallized from ethanol. The physical data of the compounds (2a-j) are given in Table-1.