[NH2:1][C@@H]1C2CCN(CC2)[C@H]1CC1C=NC=CC=1.[F:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([F:27])[CH:26]=1)[C:21](O)=[O:22].C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[F:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([F:27])[CH:26]=1)[C:21]([NH2:1])=[O:22]To a suspension of (2S,3R)-3-amino-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane (20 mg, 0.092 mmol, prepared as described in PCT WO 09/018505, herein incorporated by reference with regard to such synthesis), o-(benzotriazol-1-yl)-N,N,N,1-tetramethyluronium hexafluorophosphate (HBTU, 41.7 mg, 0.110 mmol) and 3,5-difluorobenzoic acid (17.4 mg, 0.110 mmol) in N,N-dimethylformamide (DMF, 2 ml) was added triethylamine (28 mg, 0.28 mmol) at room temperature. The reaction mixture was stirred overnight at room temperature, diluted with ethyl acetate (200 ml) and washed with 20% aqueous potassium carbonate. The residue was purified by silica gel chromatography with the eluent methanol:triethylamine=300:1. The solvent was removed to give (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide (30 mg, 76%), purity by HPLC: 100% (214 nm), 98.2% (254 nm); 1H NMR (400 MHz, CDCl3) d 8.48 (d, j=2.0 Hz, 1H), 8.36 (dd, j=1.7 Hz, j=4.9 Hz, 1H), 7.56-7.60 (m, 1H), 7.14-7.20 (m, 1H), 7.05-7.14 (m, 2H), 6.87-6.96 (m, 1H), 6.23 (d, j=7.8 Hz, 1H), 3.88-3.96 (m, 1H), 3.02-3.13 (m, 1H), 2.82-3.00 (m, 4H), 2.65-2.82 (m, 2H), 1.97-2.05 (m, 1H), 1.58-1.84 (m, 3H), 1.43-1.55 (m, 1H); ESI-MS 358.1(MH)+.
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