Ammonia → 5-[6-(1-azabicyclo[2.2.2]oct-3-yloxy)pyridazin-3-yl]-1H-indole

HRID 2242832Notes

Reaction equation

HRID 2242832 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][CH:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[CH:4][CH:3]=1.[NH:17]1[C:25]2[C:20](=[CH:21][C:22](B(O)O)=[CH:23][CH:24]=2)[CH:19]=[CH:18]1.N>>[N:11]12[CH2:16][CH2:15][CH:14]([CH2:13][CH2:12]1)[CH:9]([O:8][C:5]1[N:6]=[N:7][C:2]([C:22]3[CH:21]=[C:20]4[C:25](=[CH:24][CH:23]=3)[NH:17][CH:18]=[CH:19]4)=[CH:3][CH:4]=1)[CH2:10]2

Participants

4

Reactant 3

HCID 222AmmoniaHCID 27343615-Indolylboronic acidHCID 117764033-[(6-Chloropyridazin-3-yl)oxy]quinuclidine

Product 1

HCID 114044235-[6-(1-azabicyclo[2.2.2]oct-3-yloxy)pyridazin-3-yl]-1H-indole

Procedure

The product of Example 7A (200 mg, 0.8 mmol) was coupled with 5-indolylboronic acid (161 mg, 1 mmol) according to the procedure of Example 3A. The title product was purified by preparative HPLC (Gilson, column, Symmetry® C-8 7 μm, 40×100 mm. Eluting Solvent, MeCN/H2O (with 0.2% v. TFA) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (35 mg, yield, 14%). 1H NMR (300 MHz, CD3OD) 61.50-1.65 (m, 1H), 1.70-1.93 (m, 2H), 2.00-2.16 (m, 1H), 2.29-2.37 (m, 1H), 2.78-3.05 (m, 5H), 3.44-3.55 (m, 1H), 5.26-5.35 (m, 1H), 6.56(dd, J=3.3, 1.1 Hz, 1H)), 7.25 (d, J=9.2 Hz, 1H), 7.31 (d, J=3.4 Hz, 1H), 7.51 (d, J=8.8 Hz, 1H), 7.73 (dd, J=8.5, 1.7 Hz, 1H), 8.08 (d, J=9.5 Hz, 1H), 8.14 (d, J=1.7 Hz, 1H) ppm. MS (DCI/NH3): m/z 321 (M+H)+.

Workup

  1. customThe title product was purified by preparative HPLC (Gilson, column, Symmetry® C-8 7 μm, 40×100 mm
  2. customEluting Solvent, MeCN/H2O (with 0.2% v. TFA) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (35 mg, yield, 14%)

Sources & evidence

ORD record
ord-6f837a12b0174ffe84819c47f70d16e3
Source dataset
uspto-grants-2010_03
Patent number
US07674794B2

Reaction notes

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