* 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] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
2
[ 5327-32-2 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
3
[ 142404-82-8 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
4
[ 98198-48-2 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
5
[ 695-34-1 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
6
[ 100367-40-6 ]
[ 228410-90-0 ]
Yield
Reaction Conditions
Operation in experiment
85%
With sulfuric acid; sodium nitrite In water at 0 - 100℃; for 6 h;
To a solution of 5-bromo-4-methyl-3-nitropyridin-2-amine (28 g, 121 mmol) in water (900 ml) was added H2S04 (28 ml) followed by NaN02 (20.91 g, 303 mmol) in water (100 ml) drop wise at 0°C. The reaction mixture was slowly warmed to room temperature for 2h, the reaction mixture was heated at 100°C for 4h. The solid formed in reaction mixture was filtered and dried to afford title compound as a pale yellow solid (24.0 g, 85 percent); 1H NMR (400 MHz, DMSO-de) δ 12.97 (s, 1H), 8.01 (s, 1H), 2.21 (s, 3H); LC/MS: 233 (M+l)+.
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
9
[ 6635-86-5 ]
[ 228410-90-0 ]
Reference：
[1] Patent: WO2014/125408, 2014, A2,
10
[ 5327-32-2 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
11
[ 142404-82-8 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
12
[ 98198-48-2 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
13
[ 695-34-1 ]
[ 884495-14-1 ]
[ 228410-90-0 ]
Reference：
[1] Organic Process Research and Development, 2017, vol. 21, # 8, p. 1095 - 1109
14
[ 228410-90-0 ]
[ 74-88-4 ]
[ 1446237-40-6 ]
Yield
Reaction Conditions
Operation in experiment
93%
Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5 h; Stage #2: at 20℃; for 3 h;
Step 1. 5-Bromo-1,4-dimethyl-3-nitropyridin-2(1H)-one A solution of 5-bromo-4-methyl-3-nitropyridin-2-ol (15.00 g, 64.37 mmol) [Combi-Blocks, AN-1086] in N,N-dimethylformamide (250 mL) was treated with sodium hydride (3.09 g, 77.3 mmol) (60percent dispersion on mineral oil) slowly and portionwise, and stirred at RT for 30 min. The reaction mixture was treated with methyl iodide (4.81 mL, 77.2 mmol) dropwise and stirred at RT for 3 h. LCMS indicated a clean peak for methylated product. The reaction mixture was poured over water/ice (˜400 mL) and allowed to stir while the ice melted. The aqueous mixture was extracted with EA. The organic layer was washed with water (3*) and brine, dried with magnesium sulfate, filtered, and concentrated to give the desired product (14.9 g, 93percent) that was used without further purification. LCMS calculated for C7H8BrN2O3 (M+H)+: m/z=247.0, 249.0. found: 247.0, 248.9.
93%
Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5 h; Stage #2: at 20℃; for 3 h;
Step 1. 5-Bromo-1,4-dimethyl-3-nitropyridin-2(1H)-one A solution of 5-bromo-4-methyl-3-nitropyridin-2-ol (15.00 g, 64.37 mmol) [Combi-Blocks, AN-1086] in N,N-dimethylformamide (250 mL) was treated with sodium hydride (3.09 g, 77.3 mmol) (60percent dispersion on mineral oil) slowly and portionwise, and stirred at RT for 30 min. The reaction mixture was treated with methyl iodide (4.81 mL, 77.2 mmol) dropwise and stirred at RT for 3 h. LCMS indicated a clean peak for methylated product. The reaction mixture was poured over water/ice (˜400 mL) and allowed to stir while the ice melted. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with water (3*) and brine, dried with magnesium sulfate, filtered, and concentrated to give the desired product (14.9 g, 93percent) that was used without further purification. LCMS calculated for C7H8BrN2O3 (M+H)+: m/z=247.0, 249.0. found: 247.0, 248.9.
92%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2 h;
To a solution of 5-bromo-4-methyl-3-nitropyridin-2-ol (24 g, 103 rnmol) in DMF (200 ml) was added K2CO3 (21.39 g, 155 mmol) and CH3I (21.86 g, 155 mmol). The reaction mixture was stirred at room temperature for 2h. The reaction mixture was poured into ice cold water, the solid formed was filtered and dried under vacuum to afford title compound as off white solid (23.5 g, 92 percent). FontWeight="Bold" FontSize="10" H NMR (400 MHz, DMSO-d6) δ 8.40 (s, 1H), 3.51 (s, 3H), 2.21 (s, 3H).
With sulfuric acid; sodium nitrite; In water; at 0 - 100℃; for 6h;
To a solution of <strong>[100367-40-6]5-bromo-4-methyl-3-nitropyridin-2-amine</strong> (28 g, 121 mmol) in water (900 ml) was added H2S04 (28 ml) followed by NaN02 (20.91 g, 303 mmol) in water (100 ml) drop wise at 0C. The reaction mixture was slowly warmed to room temperature for 2h, the reaction mixture was heated at 100C for 4h. The solid formed in reaction mixture was filtered and dried to afford title compound as a pale yellow solid (24.0 g, 85 %); 1H NMR (400 MHz, DMSO-de) delta 12.97 (s, 1H), 8.01 (s, 1H), 2.21 (s, 3H); LC/MS: 233 (M+l)+.
Step 1. 5-Bromo-1,4-dimethyl-3-nitropyridin-2(1H)-one A solution of <strong>[228410-90-0]5-bromo-4-methyl-3-nitropyridin-2-ol</strong> (15.00 g, 64.37 mmol) [Combi-Blocks, AN-1086] in N,N-dimethylformamide (250 mL) was treated with sodium hydride (3.09 g, 77.3 mmol) (60% dispersion on mineral oil) slowly and portionwise, and stirred at RT for 30 min. The reaction mixture was treated with methyl iodide (4.81 mL, 77.2 mmol) dropwise and stirred at RT for 3 h. LCMS indicated a clean peak for methylated product. The reaction mixture was poured over water/ice (?400 mL) and allowed to stir while the ice melted. The aqueous mixture was extracted with EA. The organic layer was washed with water (3*) and brine, dried with magnesium sulfate, filtered, and concentrated to give the desired product (14.9 g, 93%) that was used without further purification. LCMS calculated for C7H8BrN2O3 (M+H)+: m/z=247.0, 249.0. found: 247.0, 248.9.
93%
Step 1. 5-Bromo-1,4-dimethyl-3-nitropyridin-2(1H)-one A solution of <strong>[228410-90-0]5-bromo-4-methyl-3-nitropyridin-2-ol</strong> (15.00 g, 64.37 mmol) [Combi-Blocks, AN-1086] in N,N-dimethylformamide (250 mL) was treated with sodium hydride (3.09 g, 77.3 mmol) (60% dispersion on mineral oil) slowly and portionwise, and stirred at RT for 30 min. The reaction mixture was treated with methyl iodide (4.81 mL, 77.2 mmol) dropwise and stirred at RT for 3 h. LCMS indicated a clean peak for methylated product. The reaction mixture was poured over water/ice (?400 mL) and allowed to stir while the ice melted. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with water (3*) and brine, dried with magnesium sulfate, filtered, and concentrated to give the desired product (14.9 g, 93%) that was used without further purification. LCMS calculated for C7H8BrN2O3 (M+H)+: m/z=247.0, 249.0. found: 247.0, 248.9.
92%
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h;
To a solution of <strong>[228410-90-0]5-bromo-4-methyl-3-nitropyridin-2-ol</strong> (24 g, 103 rnmol) in DMF (200 ml) was added K2CO3 (21.39 g, 155 mmol) and CH3I (21.86 g, 155 mmol). The reaction mixture was stirred at room temperature for 2h. The reaction mixture was poured into ice cold water, the solid formed was filtered and dried under vacuum to afford title compound as off white solid (23.5 g, 92 %). FontWeight="Bold" FontSize="10" H NMR (400 MHz, DMSO-d6) delta 8.40 (s, 1H), 3.51 (s, 3H), 2.21 (s, 3H).
With tin(ll) chloride; In ethanol; for 12h;Reflux;
To a solution of <strong>[228410-90-0]5-bromo-4-methyl-3-nitropyridin-2-ol</strong> (1.0 g, 4.29 mmol) in ethanol (20 mL), at room temperature was added tin (II) chloride (2.44 g, 12.87 mmol). The resulting mixture was stirred at reflux temperature for 12 h. Then the reaction was allowed to room temperature and the solvent was removed under reduced pressure. The residue was basified with aqueous ammonia and filtered through celite. The filtrate was evaporated under vacuum to afford 180 mg (21%) of the desired product which was used for the next step without further purification. 1HNMR (400 MHz, DMSO-d6) delta 11.56 (s, 1H), 6.91 (s, 1H), 5.16 (s, 2H, D2O exchangeable), 2.06 (s, 3H); GC-MS (m/z) 202, 204 [M+, Br79, 81].
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
