Cyclobutanemethanamine, hydrochloride (1:1)

White solid

Aniine 1 : Cyclobutylmethanamine hydrochloride A solution of borane in THF (1 M, 296 mL, 296 mmol ) was added to a solution of cyclobutanecarbonitrile (20 g, 247 mmol) in THF (60 mL) under argon, and the mixture heated under reflux overnight. The mixture was cooled in an ice-water bath and MeOH (120 mL) added dropwise while keeping the temperature of the mixture below 20 °C. HCl in MeOH (4 M, 300 mL) was added, again keeping the temperature below 20 °C. The resulting solution was heated under reflux for 2.5 h. After cooling, the mixture was concentrated. The residue was diluted with MeOH (100 mL) and concentrated, and this process was repeated. Ether was added to the residue, and the mixture stirred for 30 minutes before filtering to give the title compound (25.9 g, 86percent) as a white solid. NMR (300 MHz, DMSO-J, , ) 6 ppm 1 .70- 1 .86 (m. 41 1) 1 .97-2.04 (m, 211 ) 2.46-2.6 1 (m, 1 H) 2.75-2.84 (m, 2H) 8.02 (br s, 3H)A solution of borane in THF (1M, 296 mL, 296 mmol) was added to a solution of cyclobutanecarbonitrile (20 g, 247 mmol) in THI (60 niL) under argon, and the mixture heated under reflux overnight. The mixture was cooled in an ice-water bath and MeOH (120 niL) added dropwise while keeping the temperature of the mixture below 20 C. HCI inMeOH (4M, 300 mL) was added, againkeeping the temperature below 20 C. The resulting solutionwas heated under reflux for 2.5 h. After cooling, the mixture was concentrated. The residue was diluted with MeOH (100 niL) and concentrated, and this process was repeated. Ether was added to the residue and the mixture stirred for 30 minutes before filtering to give the title compound (25.9 g, 86percent) as a white solid. H NNR (300 MHz, DMSO-d6) ppm 1.70-1.86 (m, 4H) 1.97-2.04 (m, 2H) 2, 46-2.61 (m, lH) 2.75-2.84 (m, 2H) 8.02 (br s, 3H)Example 91-(cyclobutylmethyl)-4-{[6-cyclopropyl-1-methy 4-(trifluoromethyl)-1H-benzimyl]carbonyl}-2-piperazinon eStep A(cyclobutylmethyl)amine hydrochloride[00159] Borane-tetrahydrofuran complex (1 M in tetrahydrofuran) (68.8 mL, 68.8 mmol) was added slowly dropwise over 15 minutes to a solution of cyclobutanecarbonitrile (4.65 g, 57.3 mmol) in tetrahydrofuran (15 mL). The mixture was heated at reflux for 16 hours and then cooled to room temperature. Methanol (75 mL) was added slowly dropwise over 15 minutes. The mixture was cooled to 5 °C in an ice bath before gaseous hydrogen chloride was bubbled in for 30 minutes. The mixture was allowed to warm to room temperature and then refluxed for 90 minutes. The mixture was allowed to cool to room temperature and concentrated. The residue was co-evaporated 2 times with methanol and concentrated. Ethyl ether was added and solids collected by filtration. The solids were taken up in hot isopropanol, filtered, and hot acetonitrile added to the filtrate. Solids formed upon cooling and were collected by filtration. The product was dried under vacuum to give the title compound (1.1g, 16percent). H NMR (DMSO-cfe) δ ppm 8.08 (br. s., 3 H), 2.79 (d, 2 H), 2.51 - 2.61 (m, 1 H), 1.94 - 2.07 (m, 2 H), 1.65 - 1.89 (m, 4 H).