Category: 1386861-46-6

Some common heterocyclic compound, 1386861-46-6, name is 2-Chloro-6-methyl-N-phenylbenzamide, molecular formula is C14H12ClNO, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. COA of Formula: C14H12ClNO

General procedure: 00685] To a stirred mixture of amide (E-2) (173 mmol, 1 eq) in anhydrous THF (250 mL) at -30 C under an argon atmosphere, a solution of n-butyllithium in hexanes (432 mol, 2.5 eq) is added dropwise over 30 min while keeping inner temperature between -30 C and -10 C. The resulting mixture is then stirred at -30 C for 30 min.[00686] To a stirred mixture of (S)-tert-butyl l-(methoxy(methyl)amino)-l-oxopropan-2- ylcarbamate (260 mmol, 1.5 eq) in anhydrous THF (250 mL) at -30 C under an argon atmosphere, a solution of isopropylmagnesium chloride in THF (286 mmol, 1.65 eq) is added dropwise over 30 min while keeping inner temperature between -30 C and -10 C. The resulting mixture is stirred at -30 C for 30 min. This solution is then slowly added to above reaction mixture while keeping the inner temperature between -30 C and -10 C. The resulting mixture is stirred at – 15 C for 1 h. The reaction mixture is quenched with water (50 mL) and then acidified with cone. HC1 at -10 C – 0 C to adjust the pH to 1-3. The mixture is allowed to warm to RT and concentrated in vacuo. The residue is dissolved in MeOH (480 mL), and then cone. HC1 (240 mL) is added quickly at RT. The resulting mixture is stirred at reflux for 1 h. The reaction mixture is concentrated in vacuo to reduce the volume to about 450 mL. The residue is extracted with a 2: 1 mixture of heptane and ethyl acetate (2 x 500 mL). The aqueous layer is basified with concentrated ammonium hydroxide to adjust the pH to 9-10 while keeping the inner temperature between -10 C and 0 C. The mixture is then extracted with DCM (3 x 300 mL), washed with brine, dried over MgSC>4 and filtered. The filtrate is concentrated in vacuo and the residue is dissolved in MeOH (1200 mL) at RT. To this solution, D- (-) – tartaric acid (21g, 140 mmol, 0.8 eq) is added in one portion at RT. After stirring at RT for 30 min, white solid precipitates out and the mixture is slurried at RT for 10 h. The solid is collected by filtration and rinsed with MeOH (3 x 50 mL). The collected solid is suspended in water (500 mL) and then neutralized with concentrated ammonium hydroxide solution at RT to adjust the pH to 9-10. The mixture is extracted with DCM (3 x 200 mL). The combined organic layers are washed with brine, dried over MgS04 and filtered. The filtrate is concentrated in vacuo to afford (S)-3-(l -aminoethyl)-isoquinolin- 1 (2H)-ones (E-3).Amine 1-1 was prepared according to Method E and then coupled to (A-3) using Method I to provide compound 1-2. ESI-MS m/z: 428.0 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1386861-46-6, its application will become more common.

Reference:
Patent; INFINITY PHARMACEUTICALS INC.; INTELLIKINE, LLC; CASTRO, Alfredo, C.; EVANS, Catherine, A.; JANARDANANNAIR, Somarajannair; LESCARBEAU, Andre; LIU, Tao; SNYDER, Daniel, A.; TREMBLAY, Martin, R.; REN, Pingda; LIU, Yi; LI, Liansheng; CHAN, Katrina; WO2013/12915; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1386861-46-6, name is 2-Chloro-6-methyl-N-phenylbenzamide belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 2-Chloro-6-methyl-N-phenylbenzamide

General procedure: To a stirred mixture of amide (C-2) (173 mmol, 1 eq) in anhydrous THF (250 mL) at -30 C under an argon atmosphere, a solution of n-butyllithium in hexanes (432 mol, 2.5 eq) is added dropwise over 30 min while keeping inner temperature between -30 C and -10 C. The resulting mixture is then stirred at -30 C for 30 min.[00540] To a stirred mixture of (S)-tert-butyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate(260 mmol, 1.5 eq) in anhydrous THF (250 mL) at -30 C under an argon atmosphere, a solution of isopropylmagnesium chloride in THF (286 mmol, 1.65 eq) is added dropwise over 30 min while keeping inner temperature between -30 C and -10 C. The resulting mixture is stirred at -30 C for 30 min. This solution is then slowly added to the above reaction mixture while keeping the inner temperature between -30 C and -10 C. The resulting mixture is stirred at -15 C for 1 h. The reaction mixture is quenched with water (50 mL) and then acidified with cone. HCl at -10 C – 0 C to adjust the pH to 1-3. The mixture is allowed to warm to RT and concentrated in vacuo. The residue is dissolved in MeOH (480 mL), and then cone. HCl (240 mL) is added quickly at RT. The resulting mixture is stirred at reflux for 1 h. The reaction mixture is concentrated in vacuo to reduce the volume to about 450 mL. The residue is extracted with a 2: 1 mixture of heptane and ethyl acetate (2 x 500 mL). The aqueous layer is basified with concentrated ammonium hydroxide to adjust the pH to 9-10 while keeping the inner temperature between -10 C and 0 C. The mixture is then extracted with DCM (3 x 300 mL), washed with brine, dried over MgSO4 and filtered. The filtrate is concentrated in vacuo and the residue is dissolved in MeOH (1200 mL) at RT. To this solution, D-(-)-tartaric acid (21g, 140 mmol, 0.8 eq) is added in one portion at RT. After stirring at RT for 30 min, a precipitate forms and the mixture is slurried at RT for 10 h. The solid is collected by filtration and rinsed with MeOH (3 x 50 mL). The collected solid is suspended in water (500 mL) and then neutralized with concentrated ammonium hydroxide solution at RT to adjust the pH to 9-10. The mixture is extracted with DCM (3 x 200 mL). The combined organic layers are washed with brine, dried over MgS04 and filtered. The filtrate is concentrated in vacuo to afford (S)-3-(1-aminoethyl)-isoquinolin-1(2H)-ones (C-3).

The synthetic route of 1386861-46-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; INFINITY PHARMACEUTICALS INC.; INTELLIKINE, LLC; CASTRO, Alfredo, C.; EVANS, Catherine, A.; LESCARBEAU, Andre; LIU, Tao; SNYDER, Daniel, A.; TREMBLAY, Martin, R.; REN, Pingda; LIU, Yi; LI, Liansheng; CHAN, Katrina; WO2013/12918; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 1386861-46-6, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1386861-46-6, name is 2-Chloro-6-methyl-N-phenylbenzamide belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Under an inert atmosphere, to a mixture of Example 2b (13.7 g, 55.9 mmol) in THF (100 mL) was added n-BuLi (2.5 mol/L, 44.7 mL, 111.8 mmoL) dropwise over 30 mm at -30C, which was stirred at room temperature for 1 hour. The resulting solution was used for next step directly. To a solution of Example 2c (cas: 87694-49-3, 19.5 g, 83.9 mmol) in THF (100 mL) was added i-PrMgC1 (1 mol/L, 92.2 mL, 92.2 mmol) dropwise over 30 mm. The reaction mixture was stirred at -3 0C for 1 hour, which was then added to the above mixture dropwise at -3 0C. The resulted solution was stirred at -15C for 3 hours, and then quenched with water (120 mL), followed by addition of EtOAc (300 mL). The organic layer was washed with NH4C1 (sat.), and brine, and concentrated in vacuo to give yellowish oil, which was used for next step directly without further purification. To the solution of above yellowish oil in methanol (90 mL) was added concentrated HC1 (90 mL) at room temperature. The resulting solution was stirred at 95C for 16 hours and then cooled to room temperature. The mixture was washed with brine, and concentrated in vacuo. The residue was extracted with EtOAc, and the organic layers were basified with NaHCO3 powder to pH = 8.5, and then extracted with DCM. The combined organic phases were washed with brine, concentrated and the residue was purified by silica gel chromatography (DCM/MeOH = 10/1) to give the desired product Example 2d (8.0 g, yield 48%) as a light yellow solid.?HNMR (400 MHz, Chloroform-d) 7.47 (m, 6H), 7.26 (d, J= 6.7 Hz, 2H), 6.70 (s, 1H), 3.70 (q, J 6.5 Hz, 1H), 1.25 (d, J 6.5 Hz, 3H).

The synthetic route of 2-Chloro-6-methyl-N-phenylbenzamide has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FRONTHERA U.S. PHARMACEUTICALS LLC; JIN, Bohan; DONG, Qing; HUNG, Gene; (106 pag.)WO2019/28395; (2019); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics