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

HRID 1441446Notes

Reaction equation

HRID 1441446 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

4

Reactant 3

HCID 222AmmoniaHCID 184508515-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)-1H-indoleHCID 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.

Workup

  1. customThe 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)
  2. customto provide
  3. customa solid (79.7 mg, yield, 24.8%)

Sources & evidence

ORD record
ord-ff0c2aff232c47679b12f000a685015d
Source dataset
uspto-grants-2010_02
Patent number
US07655657B2

Reaction notes

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