1-Boc-3-(Aminomethyl)azetidine

To a stirred solution of the nitrile (47) (728 mg, 1 equiv.) in MeOH (5 mL) was added NH3 (2M in MeOH, 10 mL) and raney nickel (1 mL). The solution was evacuated, placed under a H2 atmosphere (40 atm) and stirred at rt for 3.5 h. The suspension was then filtered through celite and washed with MeOH. The filtrate was concentrated under reduced pressure to afford the desired primary amine (48).[0185] Following general procedure 11, to a cold (0 C.), stirred solution of the amine (48) (100 mg, 1 equiv.) and Et3N (0.12 mL, 1.5 equiv.) in CH2Cl2 (5 mL) was added benzenesulfonyl chloride (0.08 mL, 1.1 equiv.). The resultant mixture was stirred at rt for 16 h. The mixture was then diluted with EtOAc and washed successively with 10% citric acid, H2O and brine. The organic extract was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution: 30% EtOAc in hexane to 50% EtOAc in hexane) to afford the desired coupled product. The N-Boc group of the coupled product was then converted to the cyanamide (N-CN) following general procedure 3 (i.e. successive treatment with TFA and BrCN). The crude material was purified by flash chromatography (gradient elution: 30% EtOAc in hexane to 67% EtOAc in hexane) to afford the desired solid N-[(1-cyano-3-azetidinyl)methyl]benzenesulfonamide (50).tert-Butyl 3-(aminomethyl)azetidine-l-carboxylate (300 mg, 1.0 equiv) and pyridine (1 mL) were combined in DCM (20 mL) at 0C. MsCl (1.1 equiv) was added dropwise. The mixture was stirred at 0C for 3h. The reaction mixture was diluted with DCM (30 mL), washed with 3x30 mL 1N HC1, water, and brine to afford /er/-butyl 3- (0609) (methylsulfonamidomethyl)azetidine-l-carboxylate (390 mg, yield 91%) which was used without further purification.Compound 7 (150 mg, 0.4 mmol) and compound 42 (91 mg, 0.6 mmol) were dissolved in 2 mL of THF.Triethylamine (202 mg, 2.0 mmol) was added dropwise at room temperature for 5 minutes, and water (10 mL) was added.Ethyl acetate was extracted twice, dried over anhydrous sodium sulfate, concentrated, and petroleum ether was taken over ethyl acetate (8:1).Compound 43 (192 mg, 95%) was obtained as white solid.

Molecular Weight:186.25
XLogP3:0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:186.136827821
Monoisotopic Mass:186.136827821
Topological Polar Surface Area:55.6
Heavy Atom Count:13
Complexity:192
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes