1-(3-bromopropyl)-pyrrolidine, hydrobromide

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

Procedure: The entitled compound was obtained as a yellow solid, according to the same method as in Example 4-(c) or according to a method similar to it but using 4-benzyl-9-(4-hydroxyphenyl)-1-oxa-4,9-diazaspiro[5,5]undecan-3-one produced in Example 4-19-(b) and 1-(3-bromopropyl)pyrrolidine hydrobromide produced according to a method described in a patent (U.S. Pat. No. 4,751,302). The entitled compound was obtained as a yellow solid produced

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

Procedure: The same procedures for preparing 1-(3-diethylaminopropyl)-3-amino-4-chloroindazole as described in Example 89 were repeated except that 8 g of 3-phthalimidoindazole and 9.5 g of 3-bromopropylpyrrolidine hydrobromide were employed instead of the 3-phthalimido-4-chloroindazole and the 3-bromopropyldiethylamine hydrobromide, respectively. As a result, 8.2 g of 1-(3-pyrrolidinopropyl)-3-aminoindazole was obtained.

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

Procedure: The same procedures for preparing 1-(3-diethylaminopropyl)-3-amino-4-chloroindazole as described in Example 89 were repeated except that 4.78 g of 3-bromopropylpyrrolidine hydrobromide and 5.66 g of 3-amino-5-chloroindazole were employed instead of the 3-bromopropyldiethylamine hydrobromide and the 3-amino-4-chloroindazole, respectively. As a result, 4.98 g of 1-(3-pyrrolidinopropyl)-3-amino-5-chloroindazole was obtained.

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

Procedure: In a first flask, lithium diisopropylamide (2.0 M in tetrahydrofuran, 135 μL, 0.27 mmol) is added at 0° C. to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 100 mg, 0.243 mmol) in N,N-dimethyl-formamide (3 mL, solution A). In another flask, lithium diisopropylamide (2.0 M in tetrahydrofuran, 135 μL, 0.27 mmol) is added to a solution of 1-(3-bromopropyl)pyrrolidine hydrobromide (70 mg, 0.256 mmol) in N,N-dimethylformamide (2 mL, solution B). This solution is then added to solution A and the resulting mixture is stirred at room temperature over night. Water is added, and the mixture is extracted twice with dichloromethane. The combined organic layers are dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Waters Xbridge-C18, gradient of methanol in water, 0.1% TFA). Yield: 15 mg; ESI mass spectrum [M+H]+=523; Retention time HPLC: 1.15 min (V001—006). the mixture is extracted twice with dichloromethane The combined organic layers are dried over Na2SO4 concentrated under reduced pressure The residue is purified by reversed phase HPLC (Waters Xbridge-C18, gradient of methanol in water, 0.1% TFA) 1.15 min (V001—006)

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

Procedure: The same procedures for preparing 1-(3-diethylaminopropyl)-3-amino-4-chloroindazole as described in Example 89 were repeated except that 8 g of 3-phthalimidoindazole and 9.5 g of 3-bromopropylpyrrolidine hydrobromide were employed instead of the 3-phthalimido-4-chloroindazole and the 3-bromopropyldiethylamine hydrobromide, respectively. As a result, 8.2 g of 1-(3-pyrrolidinopropyl)-3-aminoindazole was obtained.

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

Procedure: The same procedures for preparing 1-(3-diethylaminopropyl)-3-amino-4-chloroindazole as described in Example 89 were repeated except that 8 g of 3-phthalimidoindazole and 9.5 g of 3-bromopropylpyrrolidine hydrobromide were employed instead of the 3-phthalimido-4-chloroindazole and the 3-bromopropyldiethylamine hydrobromide, respectively. As a result, 8.2 g of 1-(3-pyrrolidinopropyl)-3-aminoindazole was obtained.

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

Procedure: The same procedures for preparing 1-(3-diethylaminopropyl)-3-amino-4-chloroindazole as described in Example 89 were repeated except that 4.78 g of 3-bromopropylpyrrolidine hydrobromide and 5.66 g of 3-amino-5-chloroindazole were employed instead of the 3-bromopropyldiethylamine hydrobromide and the 3-amino-4-chloroindazole, respectively. As a result, 4.98 g of 1-(3-pyrrolidinopropyl)-3-amino-5-chloroindazole was obtained.

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

Procedure: The title compound was synthesized as a white solid (m.p.: 123-126° C.) by the method according to Example 63, using 3-(4-hydroxyphenyl)-6-methoxy-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one synthesized in Example 197 and 1-(3-bromopropyl)pyrrolidine hydrobromide as starting materials, followed by recrystallization (ethyl acetate/diethyl ether). followed by recrystallization (ethyl acetate/diethyl ether)

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

Procedure: The title compound was synthesized as a white solid (m.p.: 123-126° C.) by the method according to Example 63, using 3-(4-hydroxyphenyl)-6-methoxy-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one synthesized in Example 197 and 1-(3-bromopropyl)pyrrolidine hydrobromide as starting materials, followed by recrystallization (ethyl acetate/diethyl ether). followed by recrystallization (ethyl acetate/diethyl ether)

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

Procedure: Using 19 mg of 3-[(4-hydroxyphenyl)thio]-N-(3-methyl-1,2,4-thiadiazol-5-yl)-6-[(4-methyl-4H-1,2,4-triazol-3-yl)thio]pyridine-2-carboxamide obtained in Reference Example (step 3) and 13 mg of 1-(3-bromopropyl)pyrrolidine hydrobromide obtained in the step 1, 4 mg of the entitled compound was obtained as a pale yellow solid in the same method as in Example 2 or in accordance with the method or by combining it with an ordinary method. obtained in the step 1

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.833 g of 3-pyrrolidin-1-ylpropan-1-ol was dissolved in 8.4 ml of 5.1 M hydrogen bromide/acetic acid solution, and stirred overnight at 100° C. The solvent was evaporated away, the resulting residue was suspended in ethyl acetate, and the formed solid was taken out through filtration, washed with ethyl acetate and dried under reduced pressure. The above process was repeated three times to obtain 2.92 g of the entitled compound as a white solid. The solvent was evaporated away the formed solid was taken out through filtration washed with ethyl acetate dried under reduced pressure

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

Procedure: The title compound was synthesized as a white solid (m.p.:123-126° C.) by the method according to Example 63, using 3-(4-hydroxyphenyl)-6-methoxy-2-methylpyrido[3,4-d]pyrimidin-4(3H)-one synthesized in Example 197 and 1-(3-bromopropyl)pyrrolidine hydrobromide as starting materials, followed by recrystallization (ethyl acetate/diethyl ether). followed by recrystallization (ethyl acetate/diethyl ether)