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Structure of 404-90-0 * Storage: {[proInfo.prStorage]}
* 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.
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at -78℃; for 1.75 h; Stage #2: With methanol In tetrahydrofuran for 0.5 h; Heating / reflux
To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at -78° C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78° C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL.x.3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58percent). 1H NMR (400 MHz, CDCl3) δ 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.
58%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at -78℃; for 0.25 h; Stage #2: at -78℃; for 1.5 h;
To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at -78° C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78° C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL*3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58percent). 1H NMR (400 MHz, CDCl3) δ 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.
With potassium <i>tert</i>-butylate In tetrahydrofuran; methanol; water
Example 15 2-(3-Fluoro-4-methoxyphenyl)acetonitrile To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at -78° C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78° C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL*3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58percent). 1H NMR (400 MHz, CDCl3) δ 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.
Reference：
[1] Patent: US2011/98311, 2011, A1,
3
[ 351-52-0 ]
[ 143-33-9 ]
[ 404-90-0 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 1, p. 296 - 306
[2] DRP/DRBP Org.Chem.,
[3] Chemische Berichte, 1951, vol. 84, p. 150,154
4
[ 102-86-3 ]
[ 331-61-3 ]
[ 404-90-0 ]
Reference：
[1] Patent: US4178460, 1979, A,
[2] Patent: US4199595, 1980, A,
5
[ 321-28-8 ]
[ 404-90-0 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 1, p. 296 - 306
6
[ 404-90-0 ]
[ 458-09-3 ]
Reference：
[1] Chemische Berichte, 1952, vol. 85, p. 577,580
[2] DRP/DRBP Org.Chem.,
[3] Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 1, p. 296 - 306
[4] DRP/DRBP Org.Chem.,
[5] Chemische Berichte, 1952, vol. 85, p. 577,580
[6] Monatshefte fuer Chemie, 1955, vol. 86, p. 511,515
[7] European Journal of Medicinal Chemistry, 2014, vol. 87, p. 508 - 518
7
[ 404-90-0 ]
[ 452-14-2 ]
Yield
Reaction Conditions
Operation in experiment
96%
With potassium hydroxide In ethanol; water for 5 h; Reflux
3-fluoro-4-methoxyphenylacetonitrile (42 g, 0.25 mol) was heated for 5 h with a solution of 32 g of potassium hydroxide in 120 mL of ethanol and 30 mL of water. After distillation of ethanol, the residue was diluted by water to a volume of 175 mL. The solution was filtered over the charcoal and the filtrate was acidified by 50percent H2SO4. The resulting solid was filtered and dried, yield 45.0 g(96percent); M.p. 110-114 °C. MS (ESI) m/z (percent): 185.1 [M+H]+.
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 1, p. 296 - 306
[2] European Journal of Medicinal Chemistry, 2014, vol. 87, p. 508 - 518
[3] Monatshefte fuer Chemie, 1955, vol. 86, p. 511,515
[4] DRP/DRBP Org.Chem.,
[5] Chemische Berichte, 1952, vol. 85, p. 577,580
A mixture of <strong>[404-90-0]2-<strong>[404-90-0](3-fluoro-4-methoxyphenyl)acetonitrile</strong></strong> (1 g, 6.05mmol), NHi/MeOH (7N, 5 mL) and Raney-Nickel (0.1 g) in MeOH (10 mL) was stirred under Lh at 55 C overnight. The reaction mixture was filtered through Celite. The filtrate was concentrated in vacuo to afford the title compound as greenish oil (0.95 g, 92.7% yield). NMR (500 MHz, DMSO-r/d) S: 7.13 - 7.00 (m, 2H), 6.95 (d, J= 8.4 Hz, 1H), 3.80 (s, 3H), 3.01 - 2.63 (m, 2H), 2.60 (d, J= 18.7 Hz, 2H), 1.27 (br, 2H).
With potassium hydroxide; In ethanol; water; for 5h;Reflux;
3-fluoro-4-methoxyphenylacetonitrile (42 g, 0.25 mol) was heated for 5 h with a solution of 32 g of potassium hydroxide in 120 mL of ethanol and 30 mL of water. After distillation of ethanol, the residue was diluted by water to a volume of 175 mL. The solution was filtered over the charcoal and the filtrate was acidified by 50% H2SO4. The resulting solid was filtered and dried, yield 45.0 g(96%); M.p. 110-114 C. MS (ESI) m/z (%): 185.1 [M+H]+.
EXAMPLE 13 Preparation of 3-[2-(3-fluoro-4-methoxyphenyl)ethylamino]-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethylpyridinyl)-pyrazinone dihydrochloride (13-1) STR32 Starting with 3-fluoro-4-methoxyphenylacetonitrile and following the procedure described in Example 10, 13-1 was prepared. MS (FAB) 455 (M+1)+; mp: >220 C.; Analysis calculated for C23 H27 N6 O3 F1 ·2.0 HCl·0.8 CH2 Cl2; C,48.01;H,5.18;N,14.12; Found: C,48.10;H,5.05;N,13.76.
42
[ 404-90-0 ]
[ 75-26-3 ]
[ 72222-29-8 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride;
EXAMPLE 41 Preparation of alpha-Isopropyl-<strong>[404-90-0]3-fluoro-4-methoxyphenylacetonitrile</strong> A mixture of <strong>[404-90-0]3-fluoro-4-methoxyphenylacetonitrile</strong> (30 g, 0.18 mol), 2-bromopropane (27.7 g, 0.225 mol), benzyltriethylammonium chloride (2.3 g, 0.01 mol) and sodium hydroxide solution (50%, 66 ml) is heated at 55 for 1 hour and cooled. The mixture is diluted with water, extracted with ether, washed with water, 1 NHCl, water, and dried (Na2 SO4). Evaporation gives the product as a brown oil (30.7 g). NMR spectrum shows the benzylic proton as a doublet at 3.6 delta.
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride;
EXAMPLE 54 Preparation of alpha-Isopropyl-<strong>[404-90-0]3-fluoro-4-methoxyphenylacetonitrile</strong> A mixture of <strong>[404-90-0]3-fluoro-4-methoxyphenylacetonitrile</strong> (30 g, 0.18 mol), 2-bromopropane (27.7 g, 0.225 mol), benzyltriethylammonium chloride (2.3 g, 0.01 mol) and sodium hydroxide solution (50%, 66 ml) is heated at 55 for 1 hour and cooled. The mixture is diluted with water, extracted with ether, washed with water, 1 NHCl, water, and dried (Na2 SO4). Evaporation gives the product as a brown oil (30.7 g). NMR spectrum shows the benzylic proton as a doublet at 3.6 delta.
EXAMPLE 40 Preparation of 3-Fluoro-4-methoxyphenylacetonitrile A mixture of <strong>[331-61-3]4-(bromomethyl)-2-fluoroanisole</strong> (45.8 g, 0.21 mol), trihexylamine (1.4 g) and sodium cyanide (20.5 g, 0.42 mol) in water (50 ml) is heated at 60-65 C. for 18 hours. The mixture is cooled and extracted in its ether, washed with water, saturated sodium chloride solution and dried (CNa2 SO4). Evaporation of the solvent gives a solid, (33.2 g): m.p. 42-46 C.
In water;
EXAMPLE 53 Preparation of 3-Fluoro-4-methoxyphenylacetonitrile A mixture of <strong>[331-61-3]4-(bromomethyl)-2-fluoroanisole</strong> (45.8 g, 0.21 mol), trihexylamine (1.4 g) and sodium cyanide (20.5 g, 0.42 mol) in water (50 ml) is heated at 60-65 C. for 18 hours. The mixture is cooled and extracted in its ether, washed with water, saturated sodium chloride solution and dried (CNa2 SO4). Evaporation of the solvent gives a solid, (33.2 g): m.p. 42-46 C.
To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at -78 C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78 C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58%). 1H NMR (400 MHz, CDCl3) delta 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) delta 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.
58%
To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at -78 C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78 C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL*3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58%). 1H NMR (400 MHz, CDCl3) delta 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) delta 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.
With potassium tert-butylate; In tetrahydrofuran; methanol; water;
Example 15 2-(3-Fluoro-4-methoxyphenyl)acetonitrile To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at -78 C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at -78 C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL*3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58%). 1H NMR (400 MHz, CDCl3) delta 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) delta 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.
2-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperidin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-N’-(1-(4-(trifluoromethyl)phenyl)ethylidene)acetohydrazide[ No CAS ]
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