5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 23 g. (0.085 mole) of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one [Sternbach et al., J. Med. Chem. 6, 261 (1963)] and 21 g. of P2S5 in 1500 ml. of pyridine was heated rapidly to the reflux temperature and refluxed for 45 min. It was then concentrated to dryness in vacuo and the residue was treated with 150 ml. of saturated NaCl solution and extracted (thrice) with methylene chloride. The CH2Cl2 solution was washed (water), dried (MgSO4), filtered and evaporated to dryness. The residue was dissolved in 1 l. of abs EtOH treated with Darco and filtered hot. The solution was then concentrated to 200 ml. and allowed to cool giving 19 g. (78%) of yellow crystalline compound, m.p. 228-229° C. The ir and nmr support the structure. A mixture of 23 g refluxed for 45 min It was then concentrated to dryness in vacuo the residue was treated with 150 ml of saturated NaCl solution and extracted (thrice) with methylene chloride The CH2Cl2 solution was washed (water) dried (MgSO4) filtered evaporated to dryness The residue was dissolved in 1 l of abs EtOH treated with Darco filtered hot The solution was then concentrated to 200 ml to cool giving 19 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To make the 6-(o-bromophenyl) product one can follow the procedure shown by Sternbach et al., J. Med. Chem. 6, 263 (1963), for the preparation of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one using the Sandmeyer reaction followed by catalytic hydrogenation of the resulting 2-bromo-2'-nitrobenzophenone. This product, 2-amino-2'-bromobenzophenone, can be substituted in the process described by Sternbach et al. to produce 1,3-dihydro-5-(o-bromophenyl)-2H-1,4-benzodiazepin-2-one. the Sandmeyer reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 13.5 g. of 5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one in 60 ml. of concentrated sulfuric acid, a solution of 5.5 g. of potassium nitrate in 20 ml. concentrated sulfuric acid is added dropwise. The solution is then heated in a bath at 45-50° for 2 1/2 hours, cooled and poured on ice. After neutralizing with ammonia, the formed precipitate is filtered off and boiled with ethanol. A small amount of white insoluble material is then filtered off. The alcoholic solution on concentration yields crystals of 7-nitro-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one (clonazepam) which, after recrystallization from dichloromethane, melt at 238-240°. The solution is then heated in a bath at 45-50° for 2 1/2 hours cooled poured on ice the formed precipitate is filtered off A small amount of white insoluble material is then filtered off The alcoholic solution on concentration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 13.5 g. of 5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one in 60 ml. of concentrated sulfuric acid, a solution of 5.5 g. of potassium nitrate in 20 ml. concentrated sulfuric acid is added dropwise. The solution is then heated in a bath at 45-50° for 2 1/2 hours, cooled and poured on ice. After neutralizing with ammonia, the formed precipitate is filtered off and boiled with ethanol. A small amount of white insoluble material is then filtered off. The alcoholic solution on concentration yields crystals of 7-nitro-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one (clonazepam) which, after recrystallization from dichloromethane, melt at 238-240°. The solution is then heated in a bath at 45-50° for 2 1/2 hours cooled poured on ice the formed precipitate is filtered off A small amount of white insoluble material is then filtered off The alcoholic solution on concentration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 23 g. (0.085 mole) of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one [Sternbach et al., J. Med. Chem. 6, 261 (1963)] and 21 g. of P2S5 in 1500 ml. of pyridine was heated rapidly to the reflux temperature and refluxed for 45 min. It was then concentrated to dryness in vacuo and the residue was treated with 150 ml. of saturated NaCl solution and extracted (thrice) with methylene chloride. The CH2Cl2 solution was washed (water), dried (MgSO4), filtered and evaporated to dryness. The residue was dissolved in 1 l. of abs EtOH treated with Darco and filtered hot. The solution was then concentrated to 200 ml. and allowed to cool giving 19 g. (78%) of yellow crystalline compound, m.p. 228-229° C. The ir and nmr support the structure. A mixture of 23 g refluxed for 45 min It was then concentrated to dryness in vacuo the residue was treated with 150 ml of saturated NaCl solution and extracted (thrice) with methylene chloride The CH2Cl2 solution was washed (water) dried (MgSO4) filtered evaporated to dryness The residue was dissolved in 1 l of abs EtOH treated with Darco filtered hot The solution was then concentrated to 200 ml to cool giving 19 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 23 g. (0.085 mole) of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one [Sternbach et al., J. Med. Chem. 6, 261 (1963)] and 21 g. of P2S5 in 1500 ml. of pyridine was heated rapidly to the reflux temperature and refluxed for 45 min. It was then concentrated to dryness in vacuo and the residue was treated with 150 ml. of saturated NaCl solution and extracted (thrice) with methylene chloride. The CH2Cl2 solution was washed (water), dried (MgSO4), filtered and evaporated to dryness. The residue was dissolved in 1 l. of abs EtOH treated with Darco and filtered hot. The solution was then concentrated to 200 ml. and allowed to cool giving 19 g. (78%) of yellow crystalline compound, m.p. 228-229° C. The ir and nmr support the structure. A mixture of 23 g refluxed for 45 min It was then concentrated to dryness in vacuo the residue was treated with 150 ml of saturated NaCl solution and extracted (thrice) with methylene chloride The CH2Cl2 solution was washed (water) dried (MgSO4) filtered evaporated to dryness The residue was dissolved in 1 l of abs EtOH treated with Darco filtered hot The solution was then concentrated to 200 ml to cool giving 19 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To make the 6-(o-bromophenyl) product one can follow the procedure shown by Sternbach et al., J. Med. Chem. 6, 263 (1963), for the preparation of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one using the Sandmeyer reaction followed by catalytic hydrogenation of the resulting 2-bromo-2'-nitrobenzophenone. This product, 2-amino-2'-bromobenzophenone, can be substituted in the process described by Sternbach et al. to produce 1,3-dihydro-5-(o-bromophenyl)-2H-1,4-benzodiazepin-2-one. the Sandmeyer reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To make the 6-(o-bromophenyl) product one can follow the procedure shown by Sternbach et al., J. Med. Chem. 6, 263 (1963), for the preparation of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one using the Sandmeyer reaction followed by catalytic hydrogenation of the resulting 2-bromo-2'-nitrobenzophenone. This product, 2-amino-2'-bromobenzophenone, can be substituted in the process described by Sternbach et al. to produce 1,3-dihydro-5-(o-bromophenyl)-2H-1,4-benzodiazepin-2-one. the Sandmeyer reaction

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 13.5 g. of 5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one in 60 ml. of concentrated sulfuric acid, a solution of 5.5 g. of potassium nitrate in 20 ml. concentrated sulfuric acid is added dropwise. The solution is then heated in a bath at 45-50° for 2 1/2 hours, cooled and poured on ice. After neutralizing with ammonia, the formed precipitate is filtered off and boiled with ethanol. A small amount of white insoluble material is then filtered off. The alcoholic solution on concentration yields crystals of 7-nitro-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one (clonazepam) which, after recrystallization from dichloromethane, melt at 238-240°. The solution is then heated in a bath at 45-50° for 2 1/2 hours cooled poured on ice the formed precipitate is filtered off A small amount of white insoluble material is then filtered off The alcoholic solution on concentration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 23 g. (0.085 mole) of 1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepin-2-one [Sternbach et al., J. Med. Chem. 6, 261 (1963)] and 21 g. of P2S5 in 1500 ml. of pyridine was heated rapidly to the reflux temperature and refluxed for 45 min. It was then concentrated to dryness in vacuo and the residue was treated with 150 ml. of saturated NaCl solution and extracted (thrice) with methylene chloride. The CH2Cl2 solution was washed (water), dried (MgSO4), filtered and evaporated to dryness. The residue was dissolved in 1 l. of abs EtOH treated with Darco and filtered hot. The solution was then concentrated to 200 ml. and allowed to cool giving 19 g. (78%) of yellow crystalline compound, m.p. 228-229° C. The ir and nmr support the structure. A mixture of 23 g refluxed for 45 min It was then concentrated to dryness in vacuo the residue was treated with 150 ml of saturated NaCl solution and extracted (thrice) with methylene chloride The CH2Cl2 solution was washed (water) dried (MgSO4) filtered evaporated to dryness The residue was dissolved in 1 l of abs EtOH treated with Darco filtered hot The solution was then concentrated to 200 ml to cool giving 19 g