2-[(E)-4-chlorobut-2-enyl]isoindole-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trans-4-[4-(2-methyloxyphenyl)piperazinyl]-2-buten-1-yl-amine: according to the method of Example 5, N-(trans-4-chloro-2-buten-1-yl)phthalimide was reacted with 1-(2-methyloxyphenyl)piperazine to obtain N-{4-[4-(2-methyloxy-phenyl)piperazinyl]-trans-2-buten-1-yl}phthalimide, which was then reacted with hydrazine hydrate. Yield: 85.6%, hydrochloride mp: 178-180° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trans-4-[4-(5-chloro-2-methylphenyl)piperazinyl]-2-buten-1-amine: according to the method of Example 1, phthalimide potassium salt was reacted with trans-1,4-dihydro-2-butene to obtain N-(trans-4-chloro-2-buten-1-yl)phthalimide, mp: 108-110° C.; which was then reacted with 5-chloro-2-methylphenylpiperazine to obtain N-{4-[4-(5-chloro-2-methylphenyl)piperazinyl]-trans-2-buten-1-yl}phthalimide, which was then reacted with hydrazine hydrate to obtain the product. Yield: 89.3%. Hydrochloride mp: 140-142° C. 1HNMR (ppm, CDCl3) δ: 1.46 (br-s, 4H), 2.25 (s, 3H), 2.61 (br-s, 2H, NH2), 2.93 (m, 4H), 3.10 (d, J=7.0 Hz), 3.39 (d, J=6.72 Hz, 2H), 5.58 (m, 1H), 5.71 (m, 1H), 6.96 (m, 2H), 7.06 (d, J=7.84, 1H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trans-4-[4-(2-methyloxyphenyl)piperazinyl]-2-buten-1-yl-amine: according to the method of Example 5, N-(trans-4-chloro-2-buten-1-yl)phthalimide was reacted with 1-(2-methyloxyphenyl)piperazine to obtain N-{4-[4-(2-methyloxy-phenyl)piperazinyl]-trans-2-buten-1-yl}phthalimide, which was then reacted with hydrazine hydrate. Yield: 85.6%, hydrochloride mp: 178-180° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trans-4-[4-(5-chloro-2-methylphenyl)piperazinyl]-2-buten-1-amine: according to the method of Example 1, phthalimide potassium salt was reacted with trans-1,4-dihydro-2-butene to obtain N-(trans-4-chloro-2-buten-1-yl)phthalimide, mp: 108-110° C.; which was then reacted with 5-chloro-2-methylphenylpiperazine to obtain N-{4-[4-(5-chloro-2-methylphenyl)piperazinyl]-trans-2-buten-1-yl}phthalimide, which was then reacted with hydrazine hydrate to obtain the product. Yield: 89.3%. Hydrochloride mp: 140-142° C. 1HNMR (ppm, CDCl3) δ: 1.46 (br-s, 4H), 2.25 (s, 3H), 2.61 (br-s, 2H, NH2), 2.93 (m, 4H), 3.10 (d, J=7.0 Hz), 3.39 (d, J=6.72 Hz, 2H), 5.58 (m, 1H), 5.71 (m, 1H), 6.96 (m, 2H), 7.06 (d, J=7.84, 1H).

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ex-7a) Under argon, to 65.8 g of trans-1,4-dichloro-2-butene was added in portions 47 g of potassium phthalimide with mechanical stirring maintaining the temperature between 100° C. and 110° C. The reaction mixture was then stirred for 2 h keeping the temperature between 145° C. to 150° C. It was then cooled to 20° C. and extracted with 3×400 mL of ether. The ether layer was separated and stripped to give a solid. This solid was recrystallized from ethanol to yield yellow crystals of N-(trans-4-Chloro-2-butenyl)phthalimide, wt. 36 g, 61% yield. Analysis calcd. for C12H10ClNO2 (MW 237.25): C, 61.26; H, 4.29; N, 6.02; Cl, 14.94; Found C, 61.18; H, 4.30; N, 5.98; Cl, 14.62. maintaining the temperature between 100° C. and 110° C The reaction mixture was then stirred for 2 h between 145° C. to 150° C extracted with 3×400 mL of ether The ether layer was separated to give a solid This solid was recrystallized from ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as in Example 1, the N-[4-chloro(trans) 2-butenyl]phthalimide was reacted with 3-(1-piperidinomethyl)phenol, followed by hydrolysis with hydrazine to obtain 1.56 g of 4-[3-(1-piperidinomethyl)phenoxy]-(trans) 2-butenylamine. To a solution of 1 g of this amine compound in 30 ml of chloroform was added 0.9 g of the 3-chloro-4-methyl-1,2,4-benzothiadiazine-1,1-dioxide, followed by the same treatment as in Example 1 to obtain 1.57 g of white crystalline 3-[N-[4-[3-(1-piperidinomethyl)phenoxy]-(trans) 2-butenyl]amino]-4-methyl-1,2,4-benzothiadiazine-1,1-dioxide (compound 23, yield 90% ). M.p. 116°~120° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 10 g of 1,4-dichloro(trans) 2-butene in 100 ml of N,N-dimethylformamide was added 16.5 g of phthalimide potassium with ice cooling. The mixture was stirred at room temperature for 8 hours, the mixture was subjected to extraction with water-ethyl acetate, and the organic layer was distilled to remove the solvent. The residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), giving 9.6 g of N-[4-chloro(trans) 2-butenyl]phthalimide (yield 51% ). the mixture was subjected to extraction with water-ethyl acetate the organic layer was distilled to remove the solvent The residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 16.0 g of 4-(1H-imidazol-1-yl)phenol in 250 ml of dimethylformamide, is treated with 4.2 g of 60% NaH. To the suspension of the sodium salt, 23.5 g of (E)-2-[4-chloro-2-buten-1-yl)-1H-isoindole-1,3(2H)-dione is added, and the reaction mixture stirred and heated on the steam bath for 16 hours. The dimethylformamide is removed in vacuo, and the residue stirred with 250 ml of water. The insolubles are collected, washed with water, and dried. Recrystallization from ethanol gives the desired product as a solid, m.p. 170°-171° C. is added heated on the steam bath for 16 hours The dimethylformamide is removed in vacuo the residue stirred with 250 ml of water The insolubles are collected washed with water dried Recrystallization from ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trans-4-[4-(2-methyloxyphenyl)piperazinyl]-2-buten-1-yl-amine: according to the method of Example 5, N-(trans-4-chloro-2-buten-1-yl)phthalimide was reacted with 1-(2-methyloxyphenyl)piperazine to obtain N-{4-[4-(2-methyloxy-phenyl)piperazinyl]-trans-2-buten-1-yl}phthalimide, which was then reacted with hydrazine hydrate. Yield: 85.6%, hydrochloride mp: 178-180° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trans-4-[4-(5-chloro-2-methylphenyl)piperazinyl]-2-buten-1-amine: according to the method of Example 1, phthalimide potassium salt was reacted with trans-1,4-dihydro-2-butene to obtain N-(trans-4-chloro-2-buten-1-yl)phthalimide, mp: 108-110° C.; which was then reacted with 5-chloro-2-methylphenylpiperazine to obtain N-{4-[4-(5-chloro-2-methylphenyl)piperazinyl]-trans-2-buten-1-yl}phthalimide, which was then reacted with hydrazine hydrate to obtain the product. Yield: 89.3%. Hydrochloride mp: 140-142° C. 1HNMR (ppm, CDCl3) δ: 1.46 (br-s, 4H), 2.25 (s, 3H), 2.61 (br-s, 2H, NH2), 2.93 (m, 4H), 3.10 (d, J=7.0 Hz), 3.39 (d, J=6.72 Hz, 2H), 5.58 (m, 1H), 5.71 (m, 1H), 6.96 (m, 2H), 7.06 (d, J=7.84, 1H).