2,3-dichlorobenzoyl cyanide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Aminoguanidine bicarbonate (1.75 moles) was dissolved in 9.3-10.0 M sulphuric acid solution. A solution of 2,3-dichlorobenzoyl cyanide (1 mole) in acetonitrile was added and the suspension stirred at 20-30° C. for 42-48 hours. The crude product was filtered and washed with water. The solid was added to sodium hydroxide solution below 35° C., then the product was filtered, washed with water and dried at 80-90° C. to obtain 1.5 as a yellow solid in 66% yield. The crude product was filtered washed with water The solid was added to sodium hydroxide solution below 35° C. the product was filtered washed with water dried at 80-90° C.

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

実験手順: The synthesis of lamotrigine is illustrated in Reference Example 1. 2,3-Dichlorobenzoyl cyanide, which is intermediate 1.4 in that synthesis, may contain up to 10% of 2,3-dichlorobenzoic anhydride as a contaminant. When the 2,3-dichlorobenzoyl cyanide is treated with a solution of aminoguanidine bicarbonate in sulphuric acid, which is step (d) in Reference Example 1, the adduct (Z)-2-(2,3-dichlorophenyl)-2-(guanidinoimino)acetonitrile (intermediate 1.5) is produced. The anhydride contaminant can then react with the latter adduct to form (Z)-2-(2,3-dichlorophenyl)-2-[N′-(2,3-dichlorobenzoyl)guanidinoimino]acetonitrile, which is the direct precursor to compound B. Cyclisation of the precursor in propan-1-ol under reflux yields compound B. in that synthesis

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

実験手順: The synthesis of lamotrigine is illustrated in Reference Example 1. 2,3-Dichlorobenzoyl cyanide, which is intermediate 1.4 in that synthesis, may contain up to 10% of 2,3-dichlorobenzoic anhydride as a contaminant. When the 2,3-dichlorobenzoyl cyanide is treated with a solution of aminoguanidine bicarbonate in sulphuric acid, which is step (d) in Reference Example 1, the adduct (Z)-2-(2,3-dichlorophenyl)-2-(guanidinoimino)acetonitrile (intermediate 1.5) is produced. The anhydride contaminant can then react with the latter adduct to form (Z)-2-(2,3-dichlorophenyl)-2-[N′-(2,3-dichlorobenzoyl)guanidinoimino]acetonitrile, which is the direct precursor to compound B. Cyclisation of the precursor in propan-1-ol under reflux yields compound B. in that synthesis

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

実験手順: The synthesis of lamotrigine is illustrated in Reference Example 1. 2,3-Dichlorobenzoyl cyanide, which is intermediate 1.4 in that synthesis, may contain up to 10% of 2,3-dichlorobenzoic anhydride as a contaminant. When the 2,3-dichlorobenzoyl cyanide is treated with a solution of aminoguanidine bicarbonate in sulphuric acid, which is step (d) in Reference Example 1, the adduct (Z)-2-(2,3-dichlorophenyl)-2-(guanidinoimino)acetonitrile (intermediate 1.5) is produced. The anhydride contaminant can then react with the latter adduct to form (Z)-2-(2,3-dichlorophenyl)-2-[N′-(2,3-dichlorobenzoyl)guanidinoimino]acetonitrile, which is the direct precursor to compound B. Cyclisation of the precursor in propan-1-ol under reflux yields compound B. in that synthesis

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

実験手順: Reactor (0.5 L) was charged under nitrogen with acetonitrile (200 ml) and polyphosphoric acid (220 g), and the mixture was stirred for 0.5 hour to obtain an emulsion. Solid 2,3-dichlorobenzoyl cyanide (41 g, 0.2 mole; assay 97.5%) was added to the emulsion. Aminoguanidine bicarbonate (41 g, 0.3 mole; assay 99.0%) was added to the mixture in 5 equal portions during 2 hours at 30-40° C. The reaction mixture was stirred at 50° C. during 22 hours. Water (40 ml) was then added to the reaction mixture to obtain a clear homogeneous mixture. The mixture was dropped to water at slow stirring for 0.5 hour, and the precipitate was collected by filtration to give wet phosphate salt of 2,3-dichlorobenzoyl cyanide amidinohydrazone. to obtain an emulsion The reaction mixture was stirred at 50° C. during 22 hours to obtain a clear homogeneous mixture at slow stirring for 0.5 hour the precipitate was collected by filtration