tert-butyl 1,7-diazaspiro[4.4]nonane-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 3.0 g of tert-butyl 1,7-diazaspiro[4.4]nonane-1-carboxylate and 2.64 g of 4-fluoro-1-nitro-2-(propan-2-yloxy)benzene (obtained according to method 6), and 2.75 g of potassium carbonate in DMSO is stirred at ambient temperature overnight. The mixture is taken up with ethyl acetate and washed twice with 10 volumes of water. The organic phase is dried over magnesium sulfate and concentrated under vacuum. The crude product is purified on 120 g of silica, elution being carried out with dichloromethane, so as to obtain 3.40 g of 2-methylpropan-2-yl 7-[4-nitro-3-(propan-2-yloxy)phenyl]-1,7-diazaspiro[4.4]nonane-1-carboxylate in the form of a dark yellow solid. washed twice with 10 volumes of water The organic phase is dried over magnesium sulfate concentrated under vacuum The crude product is purified on 120 g of silica, elution

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

Procedure: A mixture of 3.0 g of tert-butyl 1,7-diazaspiro[4.4]nonane-1-carboxylate and 2.64 g of 4-fluoro-1-nitro-2-(propan-2-yloxy)benzene (obtained according to method 6), and 2.75 g of potassium carbonate in DMSO is stirred at ambient temperature overnight. The mixture is taken up with ethyl acetate and washed twice with 10 volumes of water. The organic phase is dried over magnesium sulfate and concentrated under vacuum. The crude product is purified on 120 g of silica, elution being carried out with dichloromethane, so as to obtain 3.40 g of 2-methylpropan-2-yl 7-[4-nitro-3-(propan-2-yloxy)phenyl]-1,7-diazaspiro[4.4]nonane-1-carboxylate in the form of a dark yellow solid. washed twice with 10 volumes of water The organic phase is dried over magnesium sulfate concentrated under vacuum The crude product is purified on 120 g of silica, elution

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of adamantan-2-ylamine (75 mg, 0.38 mmol), CDI (80 mg, 0.46 mmol), i-Pr2NEt (150 mg, 1.14 mmol) in CH2Cl2 (5 mL) was stirred at 0° C. for 1 h, and tert-butyl 1,7-diazaspiro[4.4]nonane-1-carboxylate (100 mg, 0.38 mmol) was added. The reaction mixture stirred at room temperature overnight. The solvent was removed under reduced pressure to give crude product which was purified by preparative TLC to afford tert-butyl 7-(2-adamantylcarbamoyl)-1,7-diazaspiro[4.4]nonane-1-carboxylate (136 mg, 89%). LC-MS Method 3, tR=4.24 min, m/z=404.1; 1H NMR (CDCl3) 1.39 (s, 9H), 1.48-1.52 (m, 4H), 1.62-1.71 (m, 5H), 1.71-1.81 (m, 10H), 1.81-1.88 (m, 3H), 1.89-2.01 (m, 1H), 2.93-3.12 (m, 1H), 3.21 (m, 1H), 3.28-3.49 (m, 2H), 3.55 (m, 1H), 3.68 (m, 1H), 3.88 (m, 1H), 4.46 (m, 1H). The solvent was removed under reduced pressure to give crude product which was purified by preparative TLC

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

Procedure: A solution of adamantan-2-ylamine (75 mg, 0.38 mmol), CDI (80 mg, 0.46 mmol), i-Pr2NEt (150 mg, 1.14 mmol) in CH2Cl2 (5 mL) was stirred at 0° C. for 1 h, and tert-butyl 1,7-diazaspiro[4.4]nonane-1-carboxylate (100 mg, 0.38 mmol) was added. The reaction mixture stirred at room temperature overnight. The solvent was removed under reduced pressure to give crude product which was purified by preparative TLC to afford tert-butyl 7-(2-adamantylcarbamoyl)-1,7-diazaspiro[4.4]nonane-1-carboxylate (136 mg, 89%). LC-MS Method 3, tR=4.24 min, m/z=404.1; 1H NMR (CDCl3) 1.39 (s, 9H), 1.48-1.52 (m, 4H), 1.62-1.71 (m, 5H), 1.71-1.81 (m, 10H), 1.81-1.88 (m, 3H), 1.89-2.01 (m, 1H), 2.93-3.12 (m, 1H), 3.21 (m, 1H), 3.28-3.49 (m, 2H), 3.55 (m, 1H), 3.68 (m, 1H), 3.88 (m, 1H), 4.46 (m, 1H). The solvent was removed under reduced pressure to give crude product which was purified by preparative TLC

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

Procedure: A mixture of 3.0 g of tert-butyl 1,7-diazaspiro[4.4]nonane-1-carboxylate and 2.64 g of 4-fluoro-1-nitro-2-(propan-2-yloxy)benzene (obtained according to method 6), and 2.75 g of potassium carbonate in DMSO is stirred at ambient temperature overnight. The mixture is taken up with ethyl acetate and washed twice with 10 volumes of water. The organic phase is dried over magnesium sulfate and concentrated under vacuum. The crude product is purified on 120 g of silica, elution being carried out with dichloromethane, so as to obtain 3.40 g of 2-methylpropan-2-yl 7-[4-nitro-3-(propan-2-yloxy)phenyl]-1,7-diazaspiro[4.4]nonane-1-carboxylate in the form of a dark yellow solid. washed twice with 10 volumes of water The organic phase is dried over magnesium sulfate concentrated under vacuum The crude product is purified on 120 g of silica, elution