Ammonia → 5-{2-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrimidin-5-yl}-1H-indole

HRID 1372861Notes

Reaction equation

HRID 1372861 reaction equation
Br[C:2]1[CH:3]=[N:4][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)=[N:6][CH:7]=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)[C@@H:9]([O:8][C:5]1[N:4]=[CH:3][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:7][N:6]=1)[CH2:10]2

Participants

4

Reactant 3

HCID 222AmmoniaHCID 27343615-Indolylboronic acidHCID 67070179(3R)-3-[(5-bromopyrimidin-2-yl)oxy]quinuclidine

Product 1

HCID 113016495-{2-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrimidin-5-yl}-1H-indole

Procedure

The product of Example 11A (283 mg, 1 mmol) was coupled with 5-indolylboronic acid (Aldrich, 193 mg, 1.2 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 (40 mg, yield, 12%). 1H NMR (300 MHz, CD3OD) δ 1.50–1.63 (m, 1H), 1.67–1.93 (m, 2H), 2.04–2.17 (m, 1H), 2.24–2.31 (m, 1H), 2.75–3.05 (m, 5H), 3.38–3.48 (m, 1H), 5.14–5.21 (m, 1H), 6.53 (dd, J=3.1, 0.7 Hz, 1H), 7.30 (d, J=3.1 Hz, 1H), 7.35 (dd, J=8.5, 1.7 Hz, 1H), 7.51 (dt, J=8.5, 0.7 Hz, 1H), 7.80 (dd, J=1.7, 0.7 Hz, 1H), 8.82 (s, 2H) ppm. MS (DCl/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 (40 mg, yield, 12%)

Sources & evidence

ORD record
ord-517132bc269240858a54755bed7c599e
Source dataset
uspto-grants-2007_01
Patent number
US07160876B2

Reaction notes

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