1,4-dioxa-8-azaspiro[4.5]decane-8-carbonitrile

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

実験手順: The title compound is prepared from 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile and N-hydroxy-butyramidine following a procedure analogous to that described in Intermediate 5. LC (method 13): tR=1.16 min; Mass spectrum (ESI+): m/z=254 [M+H]+.

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

実験手順: The title compound is prepared from 4-cyclopropylamino-piperidine-1-carboxylic acid tert-butyl ester and 3-fluoro-4-oxazol-5-yl-benzoic acid following a procedure analogous to that described in Intermediate 1. The cleavage of the BOC group is accomplished by using trifluoroacetic acid in dichloromethane. LC (method 14): tR=0.98 min; Mass spectrum (ESI+): m/z=330 [M+H]+.

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

実験手順: The title compound is prepared from 4-cyclopropylamino-3-methyl-piperidine-1-carboxylic acid tert-butyl ester and 4-oxazol-5-yl-benzoic acid following a procedure analogous to that described in Intermediate 1. LC (method 2): tR=0.84 min; Mass spectrum (ESI+): m/z=326 [M+H]+.

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

実験手順: The title compound is prepared from 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile and N-Hydroxy-2,2-dimethyl-propionamidine following a procedure analogous to that described in Intermediate 5. LC (method 14): tR=1.53 min; Mass spectrum (ESI+): m/z=268 [M+H]+.

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

実験手順: The title compound is prepared from 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile and N-hydroxy-isobutyramidine following a procedure analogous to that described in Intermediate 5. LC (method 6): tR=1.56 min; Mass spectrum (ESI+): m/z=254 [M+H]+.

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 0.5 M solution of zinc chloride in tetrahydrofuran (18.00 mL) is added dropwise at room temperature to a mixture of N-hydroxy-benzamidine (817 mg) and 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile (1.00 g) in ethyl acetate (20 mL). The reaction mixture is stirred at 50° C. for 3 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL). The solvents are evaporated and the crude product is purified by HPLC. TLC: rf=0.88 (silica gel, CH2Cl2/MeOH 9:1); Mass spectrum (ESI+): m/z=288 [M+H]+. cooled to room temperature The precipitate is filtered off heated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL) The solvents are evaporated the crude product is purified by HPLC

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

実験手順: The title compound is prepared from 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile and N-hydroxy-isobutyramidine following a procedure analogous to that described in Intermediate 2. LC (method 17): tR=1.56 min; Mass spectrum (ESI+): m/z=254 [M+H]+.

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

実験手順: The title compound is prepared from 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile and N-hydroxy-2,2-dimethyl-propionamidine following a procedure analogous to that described in Intermediate 2. LC (method 8): tR=1.53 min; Mass spectrum (ESI+): m/z=268 [M+H]+.

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

実験手順: The title compound is prepared from 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile and N-hydroxy-butyramidine following a procedure analogous to that described in Intermediate 2. LC (method 14): tR=1.16 min; Mass spectrum (ESI+): m/z=254 [M+H]+.

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 0.5 M solution of zinc chloride in tetrahydrofuran (18.00 mL) is added dropwise at room temperature to a mixture of N-hydroxy-benzamidine (817 mg) and 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile (1.00 g) in ethyl acetate (20 mL). The reaction mixture is stirred at 50° C. for 3 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL). The solvents are evaporated and the crude product is purified by HPLC. TLC: rf=0.88 (silica gel, CH2Cl2/MeOH 9:1); Mass spectrum (ESI+): m/z=288 [M+H]+. cooled to room temperature The precipitate is filtered off heated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL) The solvents are evaporated the crude product is purified by HPLC

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

実験手順: Bromonitrile (11.12 g) is added to a mixture of 1,4-dioxa-8-aza-spiro[4.5]decane (10.00 g) and ethyldiisopropylamine (59.92 mL) in dichloromethane (125 mL) and tetrahydrofuran (125 mL). The reaction mixture is stirred over night at room temperature. Water is added and the organic phase is separated, dried over Na2SO4 and concentrated in vacuo to give the title compound. TLC: rf=0.80 (aluminum oxide, ethyl acetate/petrol ether 3:1); Mass spectrum (ESI+): m/z=169 [M+H]+. the organic phase is separated dried over Na2SO4 concentrated in vacuo