N'-ethylpropane-1,3-diamine

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:; See reaction.notes.procedure_details.

実験手順: Prepared analogously to Example 1d from rac.-2-chloro-4-{N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]aminocarbonyl}benzoic acid, N-(3-aminopropyl)ethylamine, PFTU, and diisopropylethylamine in DMSO at ambient temperature. HPLC-MS results: retention time: 3.82 minutes; C22H25Cl2N5O2 (462.38); mass spectrum: (M−H)−=461/463/465 (chlorine isotope). HPLC-MS results

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

実験手順: 2,6-Dichloropyrazine (298 mg, 2.0 mmol) was dissolved in 25 mL dichloromethane. 1,5,7-triazabicyclo[4.4.0]dec-5-ene polystyrene (PS-TBD) (2.0 g, 5.0 mmol) was added followed by N-ethyltrimethylenediamine (194 mg, 1.90 mmol). The resulting mixture was agitated at room temperature overnight. The resin was filtered and the mother liquors were concentrated to a solid H (429 mg, 100%, mixture of isomers), which was used directly. [3-(E-3-methoxy-3-oxo-1-propen-1-yl)phenyl]boronic acid (618 mg, 3.0 mmol) and bistriphenylphosphinepalladium(II)chloride (35 mg, 0.05 mmol) were dispersed in 5 mL DMF in a reaction tube. Subsequently 1.5 mL of 2M Na2CO3 was added followed by intermediate H prepared above (429 mg, 2.0 mmol) as a solution in 5 mL DMF. The tube was sealed and the reaction mixture was heated at 85° C. for 72 hours. The reaction mixture was then filtered through a plug of celite, and the mother liquors were treated with a silica-bound sulfonic acid (Si-tosic acid), (9.5 g, 8.36 mmol). The resulting mixture was agitated for 24 hours, then the silica was isolated by filtration and washed with methanol. Intermediate I (150 mg, 88%, mixture of isomers) was eluted from the silica with 7N ammonia in methanol, and isolated by concentration of the eluant. The mixture was used directly. Intermediate I prepared above (140 mg, 0.41 mmol) was dissolved in 15 mL methanol. Amberlyst A26 (OH form) (1.5 g, 2.16 mmol) was added and the resulting mixture was agitated at room temperature for 72 hours. The resin was isolated by filtration and washed with methanol. The product was eluted from the resin using 20% formic acid in methanol, and isolated by concentration of the eluant (105 mg, 73%, mixture of isomers). The mixture was purified by preparative HPLC to provide the title compound (18.4 mg, 13%); MS analysis electrospray, 327 (M+H). The resin was filtered the mother liquors were concentrated to a solid H (429 mg, 100%, mixture of isomers), which The tube was sealed the reaction mixture was heated at 85° C. for 72 hours The reaction mixture was then filtered through a plug of celite the mother liquors were treated with a silica-bound sulfonic acid (Si-tosic acid), (9.5 g, 8.36 mmol) The resulting mixture was agitated for 24 hours the silica was isolated by filtration washed with methanol Intermediate I (150 mg, 88%, mixture of isomers) was eluted from the silica with 7N ammonia in methanol isolated by concentration of the eluant Amberlyst A26 (OH form) (1.5 g, 2.16 mmol) was added the resulting mixture was agitated at room temperature for 72 hours The resin was isolated by filtration washed with methanol The product was eluted from the resin isolated by concentration of the eluant (105 mg, 73%, mixture of isomers) The mixture was purified by preparative HPLC

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

実験手順: 9.1 g. of dibenzo[b,e]thiepin-11(6H)-one are mixed, while stirring, with 40 g. of N-ethyl-1,3-propanediamine and 250 ml. of absolute toluene and treated dropwise at 0° C. with 8.8 ml. of titanium tetrachloride. The reaction mixture is stirred at room temperature for 18 hours, then cooled and hydrolyzed with 250 ml. of water. The resulting suspension is filtered through diatomaceous earth and the aqueous phase is extracted with toluene. The combined toluene extracts are dried over sodium sulfate and evaporated under reduced pressure. Raw N-ethyl-N'-{dibenzo[b,e]thiepin-11(6H)-ylidene}-1,3-propanediamine is obtained which can be used directly in the above reaction. The reaction mixture is stirred at room temperature for 18 hours cooled The resulting suspension is filtered through diatomaceous earth the aqueous phase is extracted with toluene The combined toluene extracts are dried over sodium sulfate evaporated under reduced pressure