(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile

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

Procedure: In a similar manner to Example 6, ethyl 4-aminobicyclo[2.2.1]heptane-1-carboxylate (50.0 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (59.3 mg) were used to obtain (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.1]hept-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (79.4 mg).

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

Procedure: In a similar manner to Example 2, 2-tetrahydropyranyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (90.0 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (70.0 mg) were used to obtain (2S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonyl bicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (85.2 mg).

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

Procedure: In a similar manner to Example 2, t-butyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (100 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (90.0 mg) were used to obtain (2S)-1-[[N-(4-t-butoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (97.6 mg).

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

Procedure: In a similar manner to Example 2, t-butyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (100 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (90.0 mg) were used to obtain (2S)-1-[[N-(4-t-butoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (97.6 mg).

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

Procedure: Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (115 mg) was dissolved in N,N-dimethylformamide (1.5 mL) and diisopropylethylamine (100 μL) was added to the solution. (2S)-1-(2-Bromoacetyl)pyrrolidine-2-carbonitrile (120 mg) in N,N-dimethylformamide (1 mL) was then added dropwise at room temperature. The mixture was stirred for 2 hours at room temperature and was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1) to give (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (95.1 mg). was concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1)

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

Procedure: Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (115 mg) was dissolved in N,N-dimethylformamide (1.5 mL) and diisopropylethylamine (100 μL) was added to the solution. (2S)-1-(2-Bromoacetyl)pyrrolidine-2-carbonitrile (120 mg) in N,N-dimethylformamide (1 mL) was then added dropwise at room temperature. The mixture was stirred for 2 hours at room temperature and was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1) to give (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (95.1 mg). was concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1)

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

Procedure: Using 4-aminobicyclo[2.2.2]octane-1-carboxamide (50.0 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (56.9 mg), the same procedure was followed as in Example 1 to give (2S)-1-[[(4-carbamoylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (47.5 mg).

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

Procedure: Using 4-aminobicyclo[2.2.2]octane-1-carboxamide (50.0 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (56.9 mg), the same procedure was followed as in Example 1 to give (2S)-1-[[(4-carbamoylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (47.5 mg).

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

Procedure: In a similar manner to Example 6, ethyl 4-aminobicyclo[2.2.1]heptane-1-carboxylate (50.0 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (59.3 mg) were used to obtain (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.1]hept-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (79.4 mg).

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

Procedure: In a similar manner to Example 2, t-butyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (100 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (90.0 mg) were used to obtain (2S)-1-[[N-(4-t-butoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (97.6 mg).

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

Procedure: In a similar manner to Example 2, t-butyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (100 mg) and (2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrile (90.0 mg) were used to obtain (2S)-1-[[N-(4-t-butoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (97.6 mg).

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

Procedure: Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (115 mg) was dissolved in N,N-dimethylformamide (1.5 mL) and diisopropylethylamine (100 μL) was added to the solution. (2S)-1-(2-Bromoacetyl)pyrrolidine-2-carbonitrile (120 mg) in N,N-dimethylformamide (1 mL) was then added dropwise at room temperature. The mixture was stirred for 2 hours at room temperature and was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant: chloroform: methanol=10:1) to give (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (95.1 mg). was concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluant: chloroform: methanol=10:1)