4-AMINO-N,N-DIMETHYLBENZAMIDE

Step 2: 4-Amino-N, V-dimethyl-benzamideTo a solution of N, N-dimethyl-4-nitro benzamide (23 g, 0.1185 mol) in MeOH (200 mL) was added Pd/C 10percent> (2.3 g) in portions and the Parr reaction vessel was purged with nitrogen for 10 min. The reaction vessel was fixed in Parr shaker at 60 psi pressure for 3 h. The reaction mixture was filtered through the Celite.(R). pad and the filtrate was concentrated under reduced pressure to afford the title compound [18.0 g, 93percent]; LC-MS (ESI): Calculated mass: 164.1; Observed mass: 165.2 [M+H]A solution of N, N-dimethyl-4-nitrobenzamide (2.0 g, 10 mmol) in EtOAc (20 mL)was added to a flask containing 10percent Pd/C under a nitrogen atmosphere. Thereaction was placed under a hydrogen atmosphere, where it was shaken overnight. The reaction mixture was diluted with methanol (10 mL) filtered through a pad of Celite (pre-washed with EtOAc) then eluted with further EtOAc. The combined filtrate solvents were removed in vacuo to afford a light yellowsolid (1.69 g, 65percent).LC/MS (method A): RT = 0.41 mm; m/z= 165 [M+H]. Total run time 3.75 mins.The title compound from Step B above (0.46 g, 1.75 mmol) was dissolved in dichloromethane (2.2 mL) and treated with a 4 M solution of hydrochloric acid in 1, 4-dioxane (2.2 mL, 8.8 mmol). The mixture was stirred at room temperature for 3 h and diluted with ethyl acetate (20 mL). Saturated aqueous sodium carbonate was then added until pH10. The organic phase was separated, dried over NaTo a solution of tert-butyl 4-(dimethylcarbamoyl)phenylcarbamate (Int. 73) (1.11 g, 4.21 mmol) in AcOEt (20 ml), HCl 4M in AcOEt (18 ml, 76 mmol) was added, and the mixture stirred for 5 hours at RT. Step 2: Synthesis of 4-amino-N, N-dimethylbenzamide (Intermediate 74) To a solution of tert-butyl 4-(dimethylcarbamoyl)phenylcarbamate (Int. 73X1.1 1 g, 4.21 mmol) in AcOEt (20 ml), HC1 4M in AcOEt (18 ml, 76 mmol) was added and the mixture stirred for 5hrs at RT. The pH was adjusted at 6/7 by adding NaHCOTo a 500 ml three-mouth bottle by adding 200 ml of methylene chloride, will be under stirring 25.0g (0.18mol, 1 . 0eq) of the P-aminobenzoic acid in reaction adds the human, cooling to 10 °C the following, then adding dimethylamine hydrochloride 17.8g (0.21mol, 1 . 2eq), triethylamine 36.1g (0.36mol, 2 . 0eq), stirring 10 min later, is added in batches EDCI40.0g (0.21mol, 1 . 2eq), after stirring at room temperature for overnight. TLC detection reaction end, in the poured into a saturated sodium bicarbonate aqueous solution, ethyl acetate extraction, combined with the phase, wash once salt water, organic phase with sodium sulfate drying, filtering, turned to the raped drying Canada petroleum ether filtration, the white solid obtained product 19.0 g. Yield: 65.0percent, MP (°C) 151.0-153.0 °C, General procedure: Inan oven-dried 250 mL round-bottomed flask equipped with a stir bar was added 6.54 g of active zinc (Zn, 100.0 mmol) in 100 mL of THF. The flask was then cooled down to 0 C using an ice-bath. Next, 4-iodoaniline (10.9 g, 50.0 mmol) solution dissolved in 40.0 mL of THF was can nulated into the flask at 0 C. The resulting mixture was allowed to warm up to room temperature and stirred at ambient temperature for 24 h. The whole mixture was settleddown and then the supernatant was used for the subsequent coupling reactions. (b) Cross-coupling reaction of A; Into a 25 mL round-bottomed flask was placed 4-aminophenylzinc iodide (4.0 mL, 0.25 M in THF, 1.0 mmol)under argon atmosphere, then the flask was cooled down to 0 C using an icebath. Next, 4-methoxybenzoyl chloride (0.13 g, 0.8 mmol) was added, then stirred at 0 C for 30 min., quenched with saturated NH4Cl solution, thenextracted with ethyl acetate (3 10 mL). It was washed with saturated NaHCO3, 8percent NH4OH solutions and brine, then dried over anhydrous MgSO4.Purification by recrystallization (hexanes/ethyl ether) afforded 0.13 g of (4-aminophenyl)(4-methoxyphenyl)methanone (1c)A solution of 26.4 g of Into a 250-mL round-bottom flask was placed N, N-dimethyl-4-nitrobenzamide (16 g, 82.4 mmol), MeOH (100 mL). Then Pd/C (10% wt., 1 g) was added. The flask was evacuated and flushed three times with hydrogen. The resulting solution was stirred for 12 h at RT under an atmosphere of hydrogen. The solids were filtered out. The resulting filtrate was concentrated under vacuum. This resulted in 13 g (96%) of the title compound as a white solid. MS-ESI: 165.1 (M+l).Into a 250-mL round-bottom flask was placed N, N-dimethyl-4-nitrobenzamide (16 g, 82.4 mmol), MeOH (100 mL), and Pd/C (10% wt., 1 g). The flask was evacuated and flushed three times withhydrogen. The resulting solution was stirred for 12 h at RT under an atmosphere of hydrogen. ThePd/C catalysts were filtered out, and the filtrate was concentrated under vacuum. This resulted in13 g (96%) of the title compound as a white solid. MS-ESI: 165.1 (M+1).Into a 250-mL round-bottom flask was placed N, N-dimethyl-4-nitrobenzamide (16 g, 82.4 mmol), MeOH (100 mL). Then Pd/C (10% wt., 1 g) was added. The flask was evacuated and flushed three times with hydrogen. The resulting solution was stirred for 12 h at RT under an atmosphere of hydrogen. The solids were filtered out. The resulting filtrate was concentrated under vacuum. This resulted in 13 g (96%) of the title compound as a white solid. MS-ESI: 165.1(M+1).Compound (Int-11-b) (5.6 g, 28.84 mmol) was dissolved in ethanol (50 mL), Palladium / carbon (500 mg) was added, and the mixture was replaced with hydrogen, and reacted at room temperature for 8 hours.The reaction solution was filtered through a celite pad, and the filtrate was concentrated. The obtained solid was slurried with petroleum ether and filtered to obtain the title compound (4.5 g, yield: 95%).Step 2: 4-Amino-N, V-dimethyl-benzamideTo a solution of N, N-dimethyl-4-nitro benzamide (23 g, 0.1185 mol) in MeOH (200 mL) was added Pd/C 10%> (2.3 g) in portions and the Parr reaction vessel was purged with nitrogen for 10 min. The reaction vessel was fixed in Parr shaker at 60 psi pressure for 3 h. The reaction mixture was filtered through the Celite pad and the filtrate was concentrated under reduced pressure to afford the title compound [18.0 g, 93%]; LC-MS (ESI): Calculated mass: 164.1; Observed mass: 165.2 [M+H]+ (RT: 0.17 min).N, N-Dimethyl-4-nitrobenzamide (0.5 g, 1 eq), reduced iron powder (0.36 g, 2.5 eq.), ammonium chloride(0.35 ml, 2.5 eq.) in 20 ml of methanol The mixture was stirred with water at 70 C for 5 hours, and then subjected to water-purpuration, suction filtration, and column chromatography to give white solid10a (0.35 g, 82.7%).A solution of N, N-dimethyl-4-nitrobenzamide (2.0 g, 10 mmol) in EtOAc (20 mL)was added to a flask containing 10% Pd/C under a nitrogen atmosphere. Thereaction was placed under a hydrogen atmosphere, where it was shaken overnight. The reaction mixture was diluted with methanol (10 mL) filtered through a pad of Celite (pre-washed with EtOAc) then eluted with further EtOAc. The combined filtrate solvents were removed in vacuo to afford a light yellowsolid (1.69 g, 65%).LC/MS (method A): RT = 0.41 mm; m/z= 165 [M+H]. Total run time 3.75 mins.B-02a (2.0 g, 10.3 mmol) is dissolved in 120 mL MeOH and 10 % palladium on coal (200 mg) is added. The reaction mixture is stirred for 2 h under an atmosphere of 4 bar hydrogen. The reaction mixture is filtered and concentrated in vacuo. Yield: 1.69 g.

Molecular Weight:164.20
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:164.094963011
Monoisotopic Mass:164.094963011
Topological Polar Surface Area:46.3
Heavy Atom Count:12
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes