tert-butyl (1S,2S,5R)-2-(aminomethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Bromo-2-chloro-pyrimidine (18.4 mmol) is added to a solution of (1S,2S,5R)-2-aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (14.1 mmol) in o-xylene (30 mL). K2CO3 (42.4 mmol) and DIPEA (42.4 mmol) are added successively and the mixture is heated to 140° C. for 17 h. The mixture is cooled to RT and diluted with EtOAc (100 mL) and water (100 mL). The layers are separated and the aq. layer is extracted with DCM (100 mL). The combined organic layers are dried over MgSO4 and concentrated in vacuo. The obtained brownish solid is stirred in ether (75 mL). The suspension is filtered and washed with ether (25 mL) and the residue is dried in vacuo to give the desired product. The mixture is cooled to RT The layers are separated the aq. layer is extracted with DCM (100 mL) The combined organic layers are dried over MgSO4 concentrated in vacuo The suspension is filtered washed with ether (25 mL) the residue is dried in vacuo

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

実験手順: At 0° C. ethyl trifluoroacetate (41.9 mmol, 1.3 eq) is added to a solution of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (32.0 mmol, 1.00 eq) in THF (80 mL). The mixture is stirred at RT for 90 min and the solvents are removed in vacuo to give the desired product which is used without further purification in the next step. LC-MS: tR=0.94 min; [M+H]+=309.1. the solvents are removed in vacuo

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid. 1H-NMR (CDCl3): δ=0.19 (q, J=4.3 Hz, 1H); 0.73 (dt, J=7.7 Hz, J=5.5 Hz, 1H); 1.30-1.36 (m, 1H); 1.38-1.43 (m, 3H); 1.45 (s, 9H); 1.46-1.53 (m, 1H); 2.24 (s, 3H); 3.34-3.42 (m, 2H); 3.55-3.64 (m, 2H); 4.18 (dd, J=10.8 Hz, J=3.0 Hz, 1H); 4.47-4.62 (m, 2H); 6.36 (s, 1H); 7.76 (bs, 1H).

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid. 1H-NMR (CDCl3): δ=0.19 (q, J=4.3 Hz, 1H); 0.73 (dt, J=7.7 Hz, J=5.5 Hz, 1H); 1.30-1.36 (m, 1H); 1.38-1.43 (m, 3H); 1.45 (s, 9H); 1.46-1.53 (m, 1H); 2.24 (s, 3H); 3.34-3.42 (m, 2H); 3.55-3.64 (m, 2H); 4.18 (dd, J=10.8 Hz, J=3.0 Hz, 1H); 4.47-4.62 (m, 2H); 6.36 (s, 1H); 7.76 (bs, 1H).

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 2,3-Dihydro-thieno[3,4-b][1,4]dioxine-5-carboxylic acid. LC-MS: tR=0.96 min; [M+H]+=381.1.

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 2,3-Dihydro-benzofuran-4-carboxylic acid.

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 2,3-Dihydro-benzofuran-4-carboxylic acid.

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with Imidazo[1,2-a]pyridine-3-carboxylic acid.

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 3-Chloro-benzoic acid.

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 3-Chloro-benzoic acid.

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid (A. Andreani et al. Eur. J. Med. Chem. 1982, 17, 271-274).

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

実験手順: prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with benzofuran-4-carboxylic acid (M. A. Eissenstat et al. J. Med. Chem. 1995, 38, 3094-3105).