3,3-PENTAMETHYLENE-2-PYRROLIDINONE

Preparation 10; 2- Aza-spiro [4.5] decan- 1 -one; A 0A flask containing tert-butyl (3S)-3 -[[4- [2- [(5-iodo-2-methyl- 1 -naphthyl)oxy]-3- pyridyl]pyrimidin-2-yl] amino]piperidine- 1 -carboxylate (1.000 equiv, 0.2353 mmol, 150 mg) was charged with A solution of 2-Aza-spiro[4.5]decan-l-one (459 mg, 3 mmol) in THF (15 mL) was treated with 3.0 mL of LAH solution (IM in THF, 3 mmol). After overnight stirring at rt, heated to reflux for 15 min., cooled to rt, quenched in succession with EtOAc and sat. aq . Na2SO4 . Extracted with ether, dried over sodium sulfate and evaporated. The crude product was converted into 5-(2-Aza-spiro[4.5]dec-2-ylmethyl)-4-bromo-l-methyl-2-phenyl-l, 2-dihydro- pyrazol-3-one as described in the general procedure. LC/MS (Method B): 404 (M+l) at 2.44 min.Preparation 10; 2- Aza-spiro [4.5] decan- 1 -one; A 00C mixture of 1-cyanomethyl-cyclohexanecarboxylic acid methyl ester (4.28 g, 23.6 mmol) and cobalt (II) chloride hexahydrate (2.81 g, 11.8 mmol) in THF (80 mL) and water (40 mL) is treated portion- wise with sodium borohydride (4.47 g, 0.118 mol) and is warmed to room temperature and stirred for 48 hours under N2. The reaction is treated with 28% ammonium hydroxide (3.1 mL) and filtered through hyflo. The solvent is removed from the filtrate in vacuo and the residue is diluted with minimal water and brine and is extracted three times with 3 : 1 chlorofornrisopropanol. The organic layer is dried (Na2SO4) and the solvent is removed in vacuo to afford crude product that is purified with a 0 to 10% methanol in CH2Cl2 gradient on silica gel to afford 1.95 g (54%) of the titled product. Rf = 0.46 (9/1 CH2Cl2/methanol). MS (m/z): 154 (M+).

Molecular Weight:153.22
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:153.115364102
Monoisotopic Mass:153.115364102
Topological Polar Surface Area:29.1
Heavy Atom Count:11
Complexity:170
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes