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

HRID 1372859Notes

Reaction equation

HRID 1372859 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:9]=2)[NH:4][CH:3]=1.Cl[C:21]1[N:26]=[N:25][C:24]([O:27][C@@H:28]2[CH:33]3[CH2:34][CH2:35][N:30]([CH2:31][CH2:32]3)[CH2:29]2)=[CH:23][CH:22]=1.N>>[N:30]12[CH2:31][CH2:32][CH:33]([CH2:34][CH2:35]1)[C@@H:28]([O:27][C:24]1[N:25]=[N:26][C:21]([C:8]3[CH:9]=[C:10]4[C:5](=[CH:6][CH:7]=3)[NH:4][CH:3]=[C:2]4[CH3:1])=[CH:22][CH:23]=1)[CH2:29]2

Participants

4

Reactant 3

HCID 222AmmoniaHCID 210726073-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 86598842(3R)-3-[(6-chloropyridazin-3-yl)oxy]quinuclidine

Product 1

HCID 112329145-{6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]pyridazin-3-yl}-3-methyl-1H-indole

Procedure

The product of Example 10A (240 mg, 1 mmol) coupled with the product of Example 9A (250 mg, 1 mmol) according to the procedure in Example 8A, 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 (40 mg, yield, 12%). 1H NMR (300 MHz, CD3OD) δ 1.50–1.64 (m, 1H), 1.69–1.92 (m, 2H), 2.01–2.14 (m, 1H), 2.29–2.35 (m, 1H), 2.37 (s, 3H), 2.81–3.04 (m, 5H), 3.43–3.55 (m, 1H), 5.27–5.34 (m, 1H), 7.06 (d, J=1.4 Hz, 1H), 7.24 (d, J=9.2 Hz, 1H), 7.44 (dd, J=8.5, 0.7 Hz, 1H), 7.71 (dd, J=8.8, 2.0, Hz, 1H), 8.07–8.12 (m, 2H) ppm. MS (DCl/NH3): m/z 335 (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 (40 mg, yield, 12%)

Sources & evidence

ORD record
ord-84a3f33c6e9f41bda99cf2dc4119979c
Source dataset
uspto-grants-2007_01
Patent number
US07160876B2

Reaction notes

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