Ammonia → (3R)-3-[6-(2-Trifluoromethyl-1H-indol-5-yl)-pyridazin-3-yloxy]-1-aza-bicyclo[2.2.2]octane

Reaction equation

Cl[C:2]1[N:7]=[N:6][C:5]([O:8][C@@H:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][C:29]([C:34]([F:37])([F:36])[F:35])=[CH:28]3)O1.N>>[F:37][C:34]([F:35])([F:36])[C:29]1[NH:30][C:31]2[C:27]([CH:28]=1)=[CH:26][C:25]([C:2]1[N:7]=[N:6][C:5]([O:8][C@@H:9]3[CH:14]4[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]4)[CH2:10]3)=[CH:4][CH:3]=1)=[CH:33][CH:32]=2

Participants

Reactant 3

HCID 222Ammonia

HCID 184508515-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)-1H-indole

HCID 86598842(3R)-3-[(6-chloropyridazin-3-yl)oxy]quinuclidine

Product 1

HCID 16224702(3R)-3-[6-(2-Trifluoromethyl-1H-indol-5-yl)-pyridazin-3-yloxy]-1-aza-bicyclo[2.2.2]octane

Procedure

The product of Example 9A (198 mg, 0.826 mmol) was coupled with the product of Example 48A (345 mg, 1.11 mmol) according to the procedure of Example 26B. The title product was purified by preparative HPLC (column: Xterra™ RP-18, 5 μm, 30×100 mm; eluting solvent, NH4HCO3—NH4OH/H2O (PH=10), (v. 90/10 to 10/90 over 20 min.); flow rate, 40 mL/min.; uv, 254 nm) to provide a solid (79.7 mg, yield, 24.8%). 1H NMR (300 MHz, CD3OD) δ 1.50-1.93 (m, 3H) 1.99-2.15 (m, 1H) 2.29-2.37 (m, 1H) 2.78-3.05 (m, 5H) 3.49 (ddd, J=14.83, 8.39, 1.86 Hz, 1H) 5.27-5.36 (m, 1H) 7.01 (s, 1H) 7.27 (d, J=9.49 Hz, 1H) 7.59 (d, J=8.81 Hz, 1H) 7.94 (dd, J=8.81, 1.70 Hz, 1H) 8.11 (d, J=9.15 Hz, 1H) 8.24 (s, 1H) ppm. MS (DCI/NH3) m/z 389 (M+H)+. Anal. Calculated for C20H19F3N4O: C, 61.85; H, 4.93; N, 14.43. Found: C, 61.62; H, 4.56; N, 13.89.