Cyclobutanamine, 1-(4-bromophenyl)-, hydrochloride (1:1)

In step 2 Manufactured 1-(4-Bromophenyl)cyclobutane-1-carboxamide (8.120 g, 31.952 mmol), sodium hypochlorite (11.00percent solution, 25.101 mL, 44.733 mmol), sodium hydroxide (3.00 M solution in water, 29.822 mL, 89.466 mmol) was dissolved in 1-butanol (50 mL) at room temperature and stirred at the same temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was dissolved in ethyl acetate, and hydrochloric acid (4.00 M solution in 1, 4-dioxane, 11.982 mL, 47.928 mmol) was added and stirred. The precipitated solid was filtered, washed with ethyl acetate and dried to give the title compound (3.320 g, 39.6 percent) Was obtained in the form of a white solid.In step 2 Manufactured 1-(4-Bromophenyl)cyclobutane-1-carboxamide (8.120 g, 31.952 mmol), sodium hypochlorite (11.00percent solution, 25.101 mL, 44.733 mmol), sodium hydroxide (3.00 M solution in water, 29.822 mL, 89.466 mmol) was dissolved in 1-butanol (50 mL) at room temperature and stirred at the same temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was dissolved in ethyl acetate, and hydrochloric acid (4.00 M solution in 1, 4-dioxane, 11.982 mL, 47.928 mmol) was added and stirred. The precipitated solid was filtered, washed with ethyl acetate and dried to give the title compound (3.320 g, 39.6 percent) Was obtained in the form of a white solid.In step 2 Manufactured 1-(4-Bromophenyl)cyclobutane-1-carboxamide (8.120 g, 31.952 mmol), sodium hypochlorite (11.00% solution, 25.101 mL, 44.733 mmol), sodium hydroxide (3.00 M solution in water, 29.822 mL, 89.466 mmol) was dissolved in 1-butanol (50 mL) at room temperature and stirred at the same temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was dissolved in ethyl acetate, and hydrochloric acid (4.00 M solution in 1, 4-dioxane, 11.982 mL, 47.928 mmol) was added and stirred. The precipitated solid was filtered, washed with ethyl acetate and dried to give the title compound (3.320 g, 39.6 %) Was obtained in the form of a white solid.In step 3 Manufactured 1-(4-bromophenyl)cyclobutan-1-amine hydrochloride (3.300 g, 12.568 mmol), ethyl 2-chloropyrimidine-5-carboxylate (2.462 g, 13.196 mmol) and N, N-diisopropylethylamine (6.567 mL, 37.703 mmol) was dissolved in 1, 4-dioxane (100 mL) at room temperature and stirred at 110 C for 17 hours, and then the reaction was terminated by lowering the temperature to room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was purified by column chromatography (SiO2, 40 g cartridge; ethyl acetate / hexane = 0% to 20%) and concentrated to give the title compound (2.320 g, 49.1%) as a pale yellow solid.General procedure: 4-(Difluoromethoxy)benzene-1-sulfonyl chloride (170 mg, 0.700 mmol) was added to a solution of 1-(4-bromophenyl)cyclobutanamineHCl (184 mg, 0.7 mmol) and BEMP (384 mg, 1.400 mmol) in dimethylformamide (1.0 mL). The reaction mixturewas stirred at 70 C overnight. Methyl bromoacetate (0.133 mL, 1.400 mmol) and additional BEMP (384 mg, 1.400 mmol) wasadded and the reaction heated at 70 C overnight. The reactionwas diluted with ethyl acetate and washed with HCl (1 N) andbrine. The organic portion was dried over sodium sulfate.The residuewas purified by chromatography using 4:1 hexanes/ethyl acetateon a 40 g silica column to give methyl 2-(N-(1-(4-bromophenyl)cyclobutyl)-4-(difluoromethoxy)phenylsulfonamido)acetate as a yellow oil (200 mg, 57% yield).

Molecular Weight:262.57
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:260.99199
Monoisotopic Mass:260.99199
Topological Polar Surface Area:26
Heavy Atom Count:13
Complexity:157
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes