Sodium cyanoborohydride → 1-[(6-Fluoro-1-benzothien-3-yl)methyl]-3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine

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Sodium cyanoborohydride (13 mg, 0.20 mmol) was added to a stirred solution of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (Example 1 Step 4, 49 mg, 0.18 mmol) and 6-fluoro-1-benzothiophene-3-carbaldehyde (36 mg, 0.20 mmol) in methanol (3 mL) and acetic acid (50 μL). The reaction was stirred at room temperature for 4 hours. The solvent was removed in vacuo and the residue partitioned between sodium carbonate and ethyl acetate. The aqueous layer was extracted with further ethyl acetate and the combined organic layers washed with water and brine, dried over MgSO4 and evaporated. The residue was purified by preparative TLC (40% ethyl acetate/isohexane) to give the title compound which was treated with ethereal HCl to give the hydrochloride salt (46 mg, 59%). 1H NMR (400 MHz, CD3OD) δ 8.00–7.96 (3H, m), 7.88 (1H, s), 7.74 (1H, dd, J=2.4, 8.8 Hz), 7.43–7.37 (2H, m), 7.31–7.27 (1H, m), 4.68 (2H, s), 4.24 (2H, s), 4.16 (2H, t, J=9.7 Hz), 3.67 (2H, d, J=7.6 Hz), 3.30–3.22 (1H, m); m/z (ES+) 394 (M+H)+.

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