2,7-DIAZASPIRO[4.5]DECAN-1-ONE HYDROCHLORIDE

Preparation 44: tert-butyl 1-oxo-2, 7-diazaspiro[4, 5]decane-7-carboxylate (P44)2, 7-diazaspiro[4.5]decan-l-one hydrochloride (600 mg, 3.15 mmol), was dissolved in 30 m L of DCM. To this solution, TEA (1.98 mL, 14.18 mmol) and Boc20 (895 mg, 4.10 mmol) were added and the reaction mixture was stirred at RT for 4 hrs. Water was added and the two layers were separated; the organic layer was washed with NH4CI, dried and evaporated to obtain ferf-butyl l-oxo-2, 7- diazaspiro[4.5]decane-7-carboxylate (p44, 830 mg, y= quant.), colourless oil.MS (ES) (m/z): 255.2 [M+H]+.Preparation 47: 7-[bis(4-fluorophenyl)methyl]-2, 7-diazaspiro[4, 5]decan-1-one (P47)Chlorobis(4-fluorophenyl)methane (0.174 m L, 0.934 mmol) was added to a stirred mixture of 2, 7- diazaspiro[4.5]decan-l-one hydrochloride salt (0.15 g, 0.78 mmol) and K2C03(0.27 g, 1.95 mmol) in Acetonitrile (3 m L). The mixture was stirred for 3 hrs at reflux. The solution was diluted with EtOAc and water. The organic phase was dried and evaporated. The residue was purified by FC on silica gel (eluent: cHex to EtOAc) to afford 7-[bis(4-fluorophenyl)methyl]-2, 7-diazaspiro[4.5]decan-l-one (p47, 165 mg, y= 59%) as white foam .MS (ES) (m/z): 357.2 [M+H]+.To a solution of 2, 7-Diazaspiro[4.5]decan-1 -one (150 mg, 0.973 mmol) was dissolved in a mixture of triethylamine (0.542 mL, 3.89 mmol) and dichloromethane (10 mL), and 3-chloro-4- [(trifluoromethyl)oxy]benzenesulfonyl chloride (344 mg, 1.167 mmol) was added. After 16 h the reaction mixture was concentrated in vacuo and the resulting residue was purified by silica column chromatography on SP4 (gradient elution: 0 - 20% MeOH - DCM) to give 7-({3-chloro-4-[(trifluoromethyl)oxy]phenyl}sulfonyl)-2, 7- diazaspiro[4.5]decan-1 -one (350 mg, 0.839 mmol, 86% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) delta ppm 1 .37 - 1.49 (m, 2 H) 1.49 - 1.65 (m, 1 H) 1.65 - 1 .76 (m, 1 H) 1.88 - 2.08 (m, 2 H) 2.27 - 2.40 (m, 2 H) 3.19 (t, J=6.63 Hz, 2 H) 3.36 (d, J=1 1 .51 Hz, 1 H) 3.64 (d, J=1 1 .62 Hz, 1 H) 7.77 (s, 1 H) 7.80 - 7.87 (m, 2 H) 8.06 (dd, J=1.59, 0.82 Hz, 1 H). MS ES+ve m/z 413 (M+H).2, 7-Diazaspiro[4.5]decan-1 -one hydrogen chloride (100 mg, 0.524 mmol) was dissolved in dichloromethane (10 mL) and triethylamine (0.219 mL, 1 .573 mmol). Then, 3-fluoro-5-(trifluoromethyl)benzenesulfonyl chloride (165 mg, 0.629 mmol) was added and stirred for 17 h. The mixture was concentrated in vacuo and the resulting residue was purified by MDAP to give 7-{[3-fluoro-5-(trifluoromethyl)phenyl]sulfonyl}- 2, 7-diazaspiro[4.5]decan-1 -one (87.9 mg, 0.226 mmol, 43% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) delta ppm 1.39 - 1 .49 (m, 2 H) 1.52 - 1 .64 (m, 1 H) 1.66 - 1 .75 (m, 1 H) 1.87 - 1.97 (m, 1 H) 1.99 - 2.09 (m, 1 H) 2.29 - 2.41 (m, 2 H) 3.14 - 3.24 (m, 2 H) 3.41 (d, J=1 1 .73 Hz, 1 H) 3.68 (d, J=1 1 .89 Hz, 1 H) 7.76 (s, 1 H) 7.84 (s, 1 H) 8.01 (d, J=7.84 Hz, 1 H) 8.16 (d, J=8.55 Hz, 1 H). MS ES+ve m/z 381 (M+H).

Molecular Weight:190.67
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:2
Exact Mass:190.0872908
Monoisotopic Mass:190.0872908
Topological Polar Surface Area:41.1
Heavy Atom Count:12
Complexity:181
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes