* 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] Chemische Berichte, 1937, vol. 70, p. 1416,1419
2
[ 64-17-5 ]
[ 445-28-3 ]
[ 938-73-8 ]
Yield
Reaction Conditions
Operation in experiment
63%
With potassium hydroxide In dimethyl sulfoxide at 20℃; for 16 h;
General procedure: A mixture of 2-fluorobenzamide (1a, 69.5 mg, 0.5 mmol), MeOH (ca. 32.0 mg, 1.0 mmol), KOH (56.0 mg, 1.0 mmol) and DMSO (2.0 mL) in a 25 mL screw-capped thick-walled Pyrex tube was stirred at room temperature for 16 h, and then water (10 mL) was added to the reaction mixture with stirring, and the mixture was extracted with ethyl acetate three times (3 * 10 mL). The combined organic phases were dried over Na2SO4 overnight. The filtered solution was concentrated under reduced pressure, and the crude residue was purified by column chromatography on silica gel with the use of petroleum ether/ethyl acetate/trimethylamine (gradient mixture ratio from 6:1:0.05 to 2:1:0.05 in volume) to afford 2aa as a white solid in 80percent yield (60.7 mg).
Reference：
[1] Tetrahedron, 2018, vol. 74, # 2, p. 303 - 307
[2] European Journal of Organic Chemistry, 2018, vol. 2018, # 39, p. 5382 - 5388
3
[ 24652-66-2 ]
[ 445-28-3 ]
Yield
Reaction Conditions
Operation in experiment
83%
With [(eta.(5)-pentamethylcyclopentadienyl)Ir(H2O)3](OTf)2 In water at 110℃; for 12 h; Schlenk technique
2-Fluorobenzaldehyde oxime (69.6 mg, 0.5 mmol), [Cp * Ir (H20) 3] [0Tf] 2 (5.lmg, 0.0075mmol, (Lml) were added sequentially to a 25 ml Schlenk reaction flask. The reaction mixture was allowed to react at 110 ° C for 12 hours and then cooled to room temperature. The water was removed by rotary evaporation, and the product was isolated by column chromatography. Yield: 83percent. ArH and 2xNH), 7. 54-7.50 (m, 1 H, ArH), 7. 29-7.25 (m (3 H, (D, JcF = 247.7 mmol), 132.4 (d, JcF = 8.8 Hz), 130.123 (d, J = 6.6 Hz, 1H) (D, JcF = 2.5Hz), 124.3 (d, JcF = 2.6Hz), 123.8 (d, JcF = 14.0Hz) 116.0 (d, JcF = 22). 5Hz).
Reference：
[1] RSC Advances, 2016, vol. 6, # 43, p. 37093 - 37098
[2] Organometallics, 2012, vol. 31, # 17, p. 6482 - 6490
[3] Catalysis Science and Technology, 2014, vol. 4, # 4, p. 988 - 996
[4] Patent: CN104418682, 2016, B, . Location in patent: Paragraph 0047-0050
4
[ 446-49-1 ]
[ 445-28-3 ]
Yield
Reaction Conditions
Operation in experiment
87%
With tert.-butylhydroperoxide; ammonia; iodine In water at 100℃; for 3 h; Sealed tube; Green chemistry
General procedure: A sealed tube equipped with a magnetic stirring bar was charged with ethylarene (1, 1.0 mmol), aq NH3 (2, 25percent aq solution,10.0 mmol), I2 (1.1 mmol), and TBHP (6.0 mmol, 70percent aq solution) at r.t. The resulting mixture was heated to 100 °C for 3.0 h. After completion of the reaction (monitored by TLC), sat.Na2S2O3 solution (10 mL) was added to the reaction mixture,and it was extracted with EtOAc (2 × 20 mL). The organic layer was washed with brine solution (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on 100–200 mesh silica gel using EtOAc–n-hexane (1:2) as the eluent to obtain the corresponding benzamide 3.
With Acetaldehyde oxime; [(eta.(5)-pentamethylcyclopentadienyl)Rh(H2O)3](OTf)2 In water at 50℃; for 6 h; Schlenk technique
A solution of 2-fluorobenzonitrile (121 mg, 1 mmol), [Cp * Rh (H2O)3] [OTf]2(3.0 mg, 0.005 mmol, 0.5 molpercent), acetaldehyde oxime (65 mg, 1.1 mmol) and water (1 ml) were successively added to a 25 ml Schlenk reaction flask.The reaction mixture was reacted at 50 ° C for 6 hours, then cooled to room temperature, and the water was removed by rotary evaporation to remove the title product. The yield was 83percent
Reference：
[1] Tetrahedron Letters, 2010, vol. 51, # 12, p. 1589 - 1591
[2] RSC Advances, 2014, vol. 4, # 3, p. 1102 - 1106
[3] Journal of Organic Chemistry, 2015, vol. 80, # 8, p. 4148 - 4151
[4] New Journal of Chemistry, 2018, vol. 42, # 19, p. 15572 - 15577
[5] Catalysis Science and Technology, 2016, vol. 6, # 12, p. 4398 - 4409
[6] ChemSusChem, 2011, vol. 4, # 1, p. 104 - 111
[7] Chemistry - A European Journal, 2017, vol. 23, # 60, p. 15210 - 15221
[8] Chemistry - A European Journal, 2008, vol. 14, # 22, p. 6601 - 6605
[9] Chemistry - A European Journal, 2010, vol. 16, # 32, p. 9808 - 9817
[10] RSC Advances, 2014, vol. 4, # 108, p. 63466 - 63474
[11] Patent: CN104744288, 2017, B, . Location in patent: Paragraph 0040; 0041; 0042; 0043
[12] Organometallics, 2011, vol. 30, # 20, p. 5442 - 5451
[13] ChemCatChem, 2017, vol. 9, # 7, p. 1349 - 1353
[14] Tetrahedron Letters, 2000, vol. 41, # 19, p. 3747 - 3749
[15] Organometallics, 2010, vol. 29, # 17, p. 3955 - 3965
[16] ACS Catalysis, 2014, vol. 4, # 6, p. 1901 - 1910
[17] European Journal of Medicinal Chemistry, 1990, vol. 25, # 8, p. 673 - 680
[18] Journal of Medicinal Chemistry, 2009, vol. 52, # 17, p. 5295 - 5298
[19] Tetrahedron Letters, 2010, vol. 51, # 13, p. 1639 - 1641
[20] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 24, p. 5682 - 5686
6
[ 393-52-2 ]
[ 445-28-3 ]
Reference：
[1] Chemische Berichte, 1937, vol. 70, p. 1416,1419
[2] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 10, p. 2544 - 2546
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 14, p. 3263 - 3270
7
[ 446-52-6 ]
[ 445-28-3 ]
[ 445-29-4 ]
Yield
Reaction Conditions
Operation in experiment
24%
Stage #1: at -33℃; for 1 h; Inert atmosphere Stage #2: at -33℃; for 1 h; Inert atmosphere; Reflux
General procedure: Under an argon atmosphere, liquid NH3 (25 mL) was condensedin a two-neck round-bottom flask immersed in a dry ice coolingbath and equipped with a dry ice reflux condenser. Aldehyde(7.34 mmol) was added, and the resulting solution (or suspension)was stirred for 1 h. KMnO4 (7.34 mmol, 1.16 g) was added,the cooling bath was removed, and the reaction mixture wasstirred for another hour with gentle reflux of NH3. Na2SO3 (22.0mmol, 2.78 g) was added, the reflux condenser was removed,and the NH3 was allowed to evaporate spontaneously. The darkbrownresidue was treated with 6 M HCl (30 mL), and theresulting precipitate was filtered, washed with H2O (100 mL)and sat. aq NaHCO3 (20 mL). All products were recrystallizedfrom EtOH.
24%
Stage #1: at -33℃; for 1 h; Inert atmosphere Stage #2: for 1 h; Inert atmosphere; Reflux
General procedure: Under an argon atmosphere, liquid NH3 (25 mL) was condensedin a two-neck round-bottom flask immersed in a dry ice coolingbath and equipped with a dry ice reflux condenser. Aldehyde (7.34 mmol) was added, and the resulting solution (or suspension)was stirred for 1 h. KMnO4 (7.34 mmol, 1.16 g) was added,the cooling bath was removed, and the reaction mixture wasstirred for another hour with gentle reflux of NH3. Na2SO3 (22.0mmol, 2.78 g) was added, the reflux condenser was removed,and the NH3 was allowed to evaporate spontaneously. The darkbrownresidue was treated with 6 M HCl (30 mL), and theresulting precipitate was filtered, washed with H2O (100 mL)and sat. aq NaHCO3 (20 mL). All products were recrystallizedfrom EtOH.
General procedure: Benzamide 4a,b (4 mmol) was added to (chlorocarbonyl)sulfenyl chloride (500 mg, 6 mmol) in toluene (30 mL). The reaction mixture was heated at reflux for 24 h. The solution was allowed to cool and the solvent was evaporated under reduced pressure. The brown solid was collected and crystallized from ethyl acetate to provide the required products as solids. Compound 5a was prepared as reported.
86%
In toluene;
(a) 5-(2-Fluorophenyl)[1,3,4]oxathiazolin-2-one Chlorocarbonyl sulfenyl chloride (11.24 g, 86 mmol) is added dropwise to a stirred suspension of <strong>[445-28-3]2-fluorobenzamide</strong> (10.80 g, 78 mmol) in dry toluene. The mixture is heated gradually over a period of 30 minutes to a temperature of about 80 C. (a clear solution is formed with evolution of gas), stirred for approximately 1 h at 80 C., heated to about 98 C., stirred at 98 C. for 5 h, and distilled to remove the toluene and excess chlorocarbonyl sulfenyl chloride. The resultant pot residue is redissolved in toluene, washed sequentially with water, 5% sodium bicarbonate and water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a residue. This residue is recrystallized from petroleum ether to give 5-(2-fluorophenyl)[1,3,4]oxathiazolin-2-one (13.2 g, 86%) as off-white crystals, mp 50 C.
86%
In toluene;
(a) 5-(2-Fluorophenyl)[1,3,4]oxathiazolin-2-one Chlorocarbonyl sulfenyl chloride (11.24 g, 86 mmol) is added dropwise to a stirred suspension of <strong>[445-28-3]2-fluorobenzamide</strong> (10.80 g, 78 mmol) in dry toluene. The mixture is heated gradually over a period of 30 minutes to a temperature of about 80C (a clear solution is formed with evolution of gas), stirred for approximately 1 h at 80C, heated to about 98C, stirred at 98C for 5 h, and distilled to remove the toluene and excess chlorocarbonyl sulfenyl chloride. The resultant pot residue is redissolved in toluene, washed sequentially with water, 5% sodium bicarbonate and water, dried over anhydrous magnesium sulfate and concentrated in vacuoto give a residue. This residue is recrystallized from petroleum ether to give 5-(2-fluorophenyl)[1,3,4]oxa-thiazolin-2-one (13.2 g, 86%) as off-white crystals, mp 50C.
(a) 2-Fluorobenzoyl isocyanate The above compound was prepared, following the procedure of Example 5a, from <strong>[445-28-3]2-fluorobenzamide</strong> (0.97 g, 6.98 mmol) and oxalyl chloride (1.08 g, 8.36 mmol) in 1,2-dichloroethane (20 ml) to give crude product (1.3 g).
In 1,2-dichloro-ethane;
(a) 2-Fluorobenzoyl isocyanate The above compound was prepared, following the procedure of Example 3a, from <strong>[445-28-3]2-fluorobenzamide</strong> (0.97 g, 6.98 mmol) and oxalyl chloride (1.08 g, 8.36 mmol) in 1,2-dichloroethane (20 ml) to give crude product (1.3 g).
In dichloromethane; at 40℃;
General procedure: Oxalyl chloride (6.61mmol) was added dropwise into a stirred solution of the appropriate benzamide (2.6mmol) in CH2Cl2 (10mL). The mixtures were heated at reflux for 20-22h. Then, solvents were evaporated in vacuo to give the respective crude benzoyl isocyanates 4a-k, which were used immediately in the next step without purification. Aminoindolin-2-one (2.8mmol) was added into a stirred solution of the appropriate benzoyl isocyanate (2.8mmol) in acetonitrile (10mL). After addition, each mixture was heated at 70-80C for 2-3h. The solid products were each filtered, washed with acetonitrile, and air dried.
In 1,2-dichloro-ethane; for 6h;Reflux; Inert atmosphere;
General procedure: Oxalylchloride (30 mmol) was added dropwise to a solution of 3 (10 mmol) in 1,2-dichloroethane(25 mL) and the mixture was heated to reflux for 6h under nitrogen atmosphere.Excess oxalylchloride and 1,2-dichloroethane was evaporated under reducedpressure to afford the crude intermediate4.
In 1,2-dichloro-ethane; at 75℃;Cooling with ice;
General procedure: The reaction of substituted benzoic acid M4 (10 mmol) with oxalyl chloride (2.52 g, 20 mmol) gavesubstituted benzoyl chloride. A solution of the substituted benzoyl chloridewas added dropwise to the solution of ammonium hydroxide (5 mL) indichloromethane (10 mL) at 0 oC. Then the reaction mixture wasstirred for 3.5 h at room temperature. Dichloromethane (10 mL) was added to themixture and the mixture was washed with water, a solution of sodium hydroxide(1 M), a solution of diluted hydrochloric acid (1 M) and brine, dried oversodiumsulfate and ltered. The solvent was evaporated under reduced pressure toget crude products. The crude products were recrystallized with dichloromethaneto give the pure compounds M5, whichwere used directly for preparation of isocyanates M6. The key intermediates isocyanates M6wereprepared by the usual method. Substituted benzamides M5 (5mmol), and to this 10mmol of oxalyl chloride was addeddropwisefor 10 min at ice-bath. After addition, the resulting clearsolution was heatedat about 75 oC for 6-8 h, and then the excessive oxalyl chloride wasremoved under reduced pressure to givea clear solution of substituted benzoylisocyanate M6, which was usedfor thenext step reaction without further purication.
In dichloromethane;Inert atmosphere; Schlenk technique; Reflux;
General procedure: The appropriate amide 32a-p, benzhydrazide (40a), or p-toluenesulfonylhydrazide (43a) (1.0 mmol, 1.0 equiv) was placed in a SchlenkKjeldahl reaction flask and the flask was evacuated/argon re-filledthree times. Subsequently, anhyd CH2Cl2 (25 mL) was added and themixture was stirred at r.t. for 10 min before dropwise addition of oxalylchloride (3.0 mmol, 3.0 equiv) followed. The reaction mixturewas then stirred at reflux for 2.5-3.0 h before cooling to r.t. and thesolvent was evaporated in vacuo. Subsequently, the appropriate nucleophile32, 34, 36, 38, 40, 42, 43, or 45 (1.1-1.25 mmol, 1.1-1.25equiv) was rapidly added and the flask was evacuated/argon re-filledbefore anhyd toluene (12 mL) was added. The reaction mixture wasthen stirred at reflux for 2.5-3 h before cooling to r.t. and concentrationto about 1/3 of the initial volume on rotavapor. Hexane was addedto the residue and the obtained precipitate (often sonicated) wascollected by filtration under reduced pressure to yield the crudeproduct. When necessary, the isolated material was purified either bycrystallization from MeOH or flash chromatography on silica gel withhexane-EtOAc as the eluent.
With Acetaldehyde oxime; [(eta.(5)-pentamethylcyclopentadienyl)Rh(H2O)3](OTf)2; In water; at 50℃; for 6h;Schlenk technique;
A solution of 2-fluorobenzonitrile (121 mg, 1 mmol), [Cp * Rh (H2O)3] [OTf]2(3.0 mg, 0.005 mmol, 0.5 mol%), acetaldehyde oxime (65 mg, 1.1 mmol) and water (1 ml) were successively added to a 25 ml Schlenk reaction flask.The reaction mixture was reacted at 50 C for 6 hours, then cooled to room temperature, and the water was removed by rotary evaporation to remove the title product. The yield was 83%
With dihydrogen peroxide; potassium carbonate; In water; dimethyl sulfoxide; at 0 - 25℃; for 0.5h;
A stirred solution of 2-fluoro-benzonitrile (0.88 g) and K2CO3 (0.15 g) in DMSO (3 mL), cooled in an ice bath, was added 35% H2O2 (1 mL). The mixture was allowed to warm up to 25 C for 30 min, poured into H2O (50 mL), and the resulting solid was collected and washed with Et2O to give 23b as white solid: mp 109-111 C (lit.7 116-119C); 1H NMR (400 MHz, Acetone-d6) delta: 7.91 (td, J = 7.7, 1.8 Hz, 1H), 7.57 (tdd, J = 7.2, 5.2, 1.9 Hz, 1H), 7.30 (tt, J = 6.2, 3.1 Hz, 1H), 7.24 (dd, J = 11.5, 8.3 Hz, 1H).
O-ethyl-2-fluoro-benzimidate tetrafluoroborate salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
In dichloromethane; at 23℃; for 16h;
A 2 liter 3-neck round bottom flask was charged with 100 g <strong>[445-28-3]2-fluorobenzamide</strong> (0.719 mol, 1 eq.). An inert atmosphere was introduced by two vacuum/argon cycles. 863 mL IM Meerwein's/CH2Cl2 solution (0.863 mol, 1.2 eq.) was then added to the flask via canula under N2 pressure, giving initially a slurry which became a clear solution after ~ 30 minutes. After ~ 4 hours stirring at 23 0C under argon, a slurry was again present. The mixture was stirred for a total of 16 hours at 23 0C under argon, then it was poured <n="22"/>quickly into a large flask and the CH2Cl2 removed at the rotovap, giving an off-white solid. This solid was then suspended in 250 rnL EtOAc, heated briefly at reflux (~ 30 seconds), then the resultant slurry was filtered while still warm under N2 on a corase- fritted funnel. After drying on the frit under a vigorous flow of N2 for one hour, 155 g 2- fluorobenzimidate 5 (84%) was obtained as a colorless solid. It was immediately bottled and placed in a desiccator. M.p. 128-1310C; 19F NMR (DMSO) delta: -113.8, -154.2 ppm.
66%
In dichloromethane; at 20℃; for 18h;
Fluoroimidate (7) and Fluoroimidazoline (8) were synthesized according to the literature. See, e.g., Busacca, C. A. et al. (2008), supra.
With sodium hydride; In DMF (N,N-dimethyl-formamide); toluene; at 20℃; for 12h;
To a stirred r. t. solution of crude [2- [DIMETHYLAMINO (METHYLTHIO) METHYLIDENE]] malono- nitrile in dry DMF (30 mL) and dry toluene (30 mL) was added 2-Fluorobenzamide (817 mg, 5.9 mmol). Sodium hydride (60% suspension in mineral oil, 470 mg, 11.7 mmol) was added portionwise. The mixture was stirred at r. t. for 12h then poured into iced water and acidified to pH 4-5 with IM HCI (aq). The two layers were separated and the aqueous layer extracted with EtOAc [(3X50] mL). The combined organic extracts were washed with brine then dried over [MGS04.] Evaporation yielded an orange oil
Example 57 In analogy to example 47, on reaction of 7-iodo-2-methyl-4-pyrrolidin-1-yl-quinoline with <strong>[445-28-3]2-fluorobenzamide</strong> there was obtained: 2-fluoro-N-(2-methyl-4-pyrrolidin-1-yl-quinolin-7-yl)-benzamide as light yellow solid. ISP mass spectrum, m/e: 350.3 (M+1 calculated for C21H20FN3O: 350).
Step 1. 2-(Piperazin-1-yl)benzamide. Refer to Chart C A mixture of <strong>[445-28-3]2-fluorobenzamide</strong> (Aldrich; 9.83 g), piperazine (Aldrich; 30.5 g), and water (135 mL) is heated at 100 C. for 26 h and at room temperature for an additional 3 days. About two-thirds of the water is then distilled off and the mixture is heated again at 100 C. overnight. After cooling, the resulting solid is collected, washed with water and toluene, and dried under reduced pressure to give 2.42 g of 2-(piperaziny-1-yl)benzamide: mp 128-134 C.; ms m/z 205; IR (mineral oil) 3322, 3274, 1595, 1665, 2815 cm-1; 1 H NMR (CDCl3) delta2.36, 3.02, 5.91, 7.23, 7.48, 8.16, 9.55.
2-chloro-3,5-bis-trifluoromethylphenylamine[ No CAS ]
[ 445-28-3 ]
1-[2-chloro-3,5-bis(trifluoromethyl)phenyl]-3-(2-fluorobenzoyl)urea[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
EXAMPLE 2 Preparation of 1-[2-chloro-3,5-bis(trifluoromethyl)phenyl]-3-(2-fluorobenzoyl)urea 2-fluorobenzoyl isocyanate was synthesised from 1.4 g of <strong>[445-28-3]2-fluorobenzamide</strong> according to the procedure described in Example 1. Then, 2.63 g of 2-chloro-3,5-bis(trifluoromethyl)aniline was added thereto in order to obtain 4.1 g (Yield 94%) of the title compound. m.p.: 140-142 C.
(1) 5 g of <strong>[445-28-3]2-fluorobenzamide</strong> and 25 ml of morpholine were reacted in an autoclave at 100 C. for 18 hours. After completion of the reaction, the reaction product was cooled, and excess morpholine was distilled off. The residue was purified by silica gel column chromatography (developing solvent; n-hexane:ethyl acetate=3:7) to obtain 2.8 g of 2-morpholinobenzamide (melting point: 112-119 C).
EXAMPLE 13 2-(5-Bromo-indolin-1-yl)benzamide A slurry was prepared from 5-bromoindoline (9.85 g, 50 mmoles) dimethylsulfoxide (DMSO) (35 ml), sodium hydride (2.6 g, 50% in oil, washed with hexane, 1.1 eq). The slurry was stirred for 30 minutes. To this a solution of <strong>[445-28-3]o-fluorobenzamide</strong> (7.9 g, 1.1 eq) in DMSO (15 ml) was added dropwise with temperature between 12-13 C. At the end of addition the reaction mixture was stirred at ambient temperature for 4 hours, then heated up to 55 C. for 24 hours. The reaction mixture was partitioned between dichloromethane (300 ml) and water (250 ml). The aqueous phase was separated and extracted twice with dichloromethane (DCM) (150 ml). The combined DCM solution was washed twice with water (100 ml), twice with 2N HCl (100 ml), twice with brine (50 ml), dried over Na2 SO4 and concentrated to a solid. Purification was on a flash chromatographic column (150 gm of silica gel) eluted with dichloromethane (DCM) (3 l). This gave 6.4 g of product (40%). Recrystallization from a small amount of ether yielded the 2-(5-bromo-indolin-1-yl)benzamide, m.p. 120-122 C. ANALYSIS: Calculated for C15 H13 BrN2 O: 56.80%C 4.13%H 8.83%N. Found: 57.09%C 4.25%H 8.90%N.
2-[3-(1-methyl-4-piperidinyl)-1H-indazol-1-yl]benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With NaH; In N,N-dimethyl-formamide;
EXAMPLE 110 2-[3-(1-Methyl-4-piperidinyl)-1H-indazol-1-yl]benzamide To a stirred suspension of NaH (4.0 g, 0.083 mol of a 50% oil dispersion) in DMF (100 ml), under nitrogen, was added, dropwise, 3-(1-methyl-4-piperidinyl)-1H-indazole (15.0, 0.07 mol) of Example 4 dissolved in hot DMF (100 ml). The reaction was stirred at ambient temperature for 0.75 hour and then <strong>[445-28-3]2-fluorobenzamide</strong> (11.6 g, 0.083 mol) was added dissolved in DMF (50 ml). The temperature of the reaction was then raised to 80 C. and kept there for 16 hours. The reaction was poured into H2 O, and the resulting solid which formed was collected and dried to yield 17.7 g. Subsequent extractive workup of the aqueous filtrate with ethyl acetate yielded an additional 2.5 g of the compound. The samples were combined and recrystallized from ethyl acetate and then from ethanol-water to yield 14.1 g (60%) of product mp 185-187 C. An analytical sample was obtained by an additional recrystallization of a 3.0 g sample from ethanol-water which resulted in 2.3 g of 2-[3-(1-methyl-4-piperidinyl)-1H-indazol-1-yl]benzamide. ANALYSIS: Calculated for C20 H22 N4 O: 71.83%C, 6.63%H, 16.75%N. Found: 71.90%C, 6.73%H, 16.72%N.
a. 2-(5-Chloro-indolin-1-yl)benzamide A slurry was prepared comprising 5-chloroindoline (15.3 gm, 0.1 mole), dimethylsulfoxide (DMSO) [50 ml] and sodium hydride (5.28 gm, 50% in oil, washed with hexane). The slurry was permitted to stir at room temperature for 1 hour. To this a solution of <strong>[445-28-3]o-fluorobenzamide</strong> (15.2 gm, 1.1 eq.) in DMSO (20 ml) was added dropwise with the temperature between 17-19 C. At the end of addition the reaction mixture was stirred at room temperature for 2 hours, then heated to 75-78 C. for 16 hours. The reaction mixture was partitioned between methylene chloride (300 ml) and water (250 ml). The aqueous phase was separated and extracted twice with methylene chloride (150 ml). The combined organic solution was washed twice with water, twice with HCl (2N, 100 ml), brine (2*50 ml), dried over Na2 SO4, concentrated to about 50 ml. Ether (50 ml) was added. The product was crystallized out upon standing overnight (about 16 hours). The yield was 14.2 gm (52%); m.p. 137-138 C. Recrystallization from methylene chloride and ether yielded 2-(5-chloro-indolin-1-yl)benzamide (11.82 gm) m.p. 137-138 C. ANALYSIS: Calculated for C15 H13 ClN2 O: 66.06%C 5.01%H 10.29%N. Found: 65.69%C 4.92%H 10.18%N.
N-(1-methoxy-2-chloroethyl)-2-fluorobenzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Example 3 Synthesis of N-(1-methoxy-2-chloroethyl)-<strong>[445-28-3]2-fluorobenzamide</strong> Utilizing a manufacturing method identical to that of preferred embodiment 2, 8.0 g of compound (2) was obtained from 10.0 g of <strong>[445-28-3]2-fluorobenzamide</strong> and 44.8 g of chloroacetaldehyde dimethyl acetal. melting point: 49.7 - 50.8C 1H - NMR (60 MHz, CDCl3, TMS) delta: 3.50 (s, 3H), 3.73 (d, 2H, J = 4.0 Hz), 5.50 - 5.85 (m, 1H), 6.95 - 7.70 (m, 4H), 7.90 - 8.29 (m, 1H)
With tetrabutylammomium bromide; ammonia; caesium carbonate; In water; for 0.333333h;Microwave irradiation;
General procedure: 1 mmol of benzoic acid, 3 ml of 25-28% aqueous ammonia, and cesium carbonate were added to a microwave reactor.0.2 mmol and 0.01 mmolTetrabutylammonium bromide was reacted at a microwave power of 120 W for 20 min.Extracted with ethyl acetate, concentrated under reduced pressure, and the product was recrystallized from ethanol.A white solid was obtained in 97% yield.
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