tert-Butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate

To a 25 ml round bottom flask were added 3-(2, 4-dioxotetrahydropyrimidin-1 (2/-/)-yl)-4- methoxybenzoic acid (intermediate 5, 100 mg, 0.38 mmol), te/ -butyl 2, 7-diazaspiro[3.5]nonane- 7-carboxylate (94 mg, 0.42 mmol), DMF (2 ml) and DIPEA (147 mg, 1 .14 mmol) at RT. HATU (174 mg, 0.46 mmol) was added and the RM was stirred at RT for 16 h. The mixture was concentrated and the residue was purified by reversed phase chromatography on an Agela C18 column (spherical 20-35 pm, 100A, 80 g) eluting with ACN in an aq. solution of ammonium hydrogen carbonate (0.05%), yielding the title compound as a solid (151 mg).Method G: Rt = 1 .90 min, MS m/z [M-55]+417.Add to tert-butyl 2, 7-azaspiro[3, 5]nonane-7-carboxylate (226 mg, 1.0 mmol) at room temperature4-trifluoromethoxyacetophenone (204 mg, 1.0 mmol) andTetraisopropyl titanate (568 mg, 2.0 mmol) was reacted at 80 C overnight.After cooling to room temperature, sodium cyanoborohydride (188 mg, 3.0 mmol) was added to the mixture, and the mixture was reacted at 40 C for 2 hours.Work-up: extraction with water and extraction with dichloromethane (20 mL x 3).The organic layer was combined, dried over anhydrous magnesium sulfate and evaporated(Ethyl acetate: petroleum ether = 1 : 2) gave pale yellow oil (150 mg).Tert-butyl 2, 7-diazaspiro[3.5]nonane-7-carboxylate 1h (2.0 g, 8.84 mmol) was dissolved in 20 mL of dichloromethane, the solution was added with benzyl chloroformate (3.06 g, 17.67 mmol) and N, N-diisopropylethylamine (4.57 g, 35.35 mmol), and reacted at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, 20 mL of ethyl acetate was added for dissolution, washed with 1M hydrochloric acid solution (10 mL) and saturated sodium chloride solution (10 mL) successively. The organic phase was concentrated under reduced pressure to obtain 2-Benzyl-7-tert-butyl-2, 7-diazaspiro[3.5]nonane-2, 7-dicarboxylate 4a (3.18 g, yellow oil), yield: 100%.

Molecular Weight:226.32
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:226.168127949
Monoisotopic Mass:226.168127949
Topological Polar Surface Area:41.6
Heavy Atom Count:16
Complexity:269
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes