Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[CH2:11][N:12]2[CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:17])=[CH:4][CH:3]=1.[N:18]1[NH:19][C:20](=[O:24])[CH:21]=[CH:22][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(O)(C)C.[Cu](I)I.O>[CH3:17][C@H:13]1[CH2:14][CH2:15][CH2:16][N:12]1[CH2:11][C@@H:9]1[CH2:10][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([N:19]2[C:20](=[O:24])[CH:21]=[CH:22][CH:23]=[N:18]2)=[CH:3][CH:4]=1A solution of the product from Example 4A (47 mg, 0.16 mmol; 1-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2S)-2-methyl-pyrrolidine), 3(2H)-pyridazinone (CAS #504-30-3, 20 mg, 0.2 mmol), copper iodide (1.5 mg, 0.008 mmol), N,N′-trans-dimethyl-cyclohexane-1,2-diamine (2.3 mg, 0.016 mmol) and potassium phosphate (75 mg, 0.35 mmol) in a mixture of toluene and isopropanol (4 ml, 1.1) was heated to 110° C. in a screw capped vial for 16 hours. The mixture was cooled to ambient temperature, treated with H2O and extracted with ethyl acetate (2×25 mL) The organic layer was separated, washed with brine and dried with magnesium sulfate. After filtration, the organic layer was concentrated under reduced pressure and the resulting oil was purified on silica gel with 1% to 3% methanol (containing 10% concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CD3OD) δ 1.07 (m, 1H), 1.14 (m, 1H), 1.26 (d, J=6 Hz, 3H), 1.40 (m, 1H), 1.58 (m, 1H), 1.90 (m, 3H), 2.13 (m, 1H), 2.58 (m, 1H), 2.70 (q, J=9 Hz, 1H), 2.89 (m, 1H), 3.14 (dd, J=12 Hz, J=6 Hz, 1H), 3.44 (m, 1H), 7.07 (d, J=9 Hz, 1H), 7.24 (d, J=9 Hz, 2H), 7.44 (d, J=9 Hz, 2H), 7.47 (m, 1H), 8.03 (m, 1H), MS (DCl—NH3) m/z 310 (M+H)+.
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