Acetic Acid → (3R)-3-[6-(3-Bromo-1H-indol-5-yl)-pyridazin-3-yloxy]-1-aza-bicyclo[2.2.2]octane

HRID 1441428Notes

Reaction equation

HRID 1441428 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10]1[N:15]=[N:14][C:13]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[NH:21][CH:20]=[CH:19]4)=[CH:12][CH:11]=1)[CH2:2]2.CC(O)=O.[Br:29]N1C(=O)CCC1=O>CC#N>[Br:29][C:19]1[C:18]2[C:22](=[CH:23][CH:24]=[C:16]([C:13]3[N:14]=[N:15][C:10]([O:9][C@@H:3]4[CH:4]5[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]5)[CH2:2]4)=[CH:11][CH:12]=3)[CH:17]=2)[NH:21][CH:20]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 67184N-bromobutanimideHCID 11151363Abt-107

Product 1

HCID 11246542(3R)-3-[6-(3-Bromo-1H-indol-5-yl)-pyridazin-3-yloxy]-1-aza-bicyclo[2.2.2]octane

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

The product of Example 9B (160 mg, 0.5 mmol) was dissolved in MeCN (10 mL) and treated with HOAc (Sigma, 60 mg, 1 mmol) for 10 min. N-bromosuccinimide (Aldrich, 110 mg, 0.6 mmol) in MeCN (Aldrich, 5 mL) was slowly added over 5 min. The mixture was stirred for 1 hour at ambient temperature and concentrated under vacuum. The title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.15) as a solid (70 mg, yield, 35%). 1H NMR (300 MHz, CD3OD) δ 1.55-1.62 (m, 1H), 1.70-1.96 (m, 2H), 2.05-2.20 (m, 1H), 2.29-2.43 (m, 1H), 2.74-3.13 (m, 5H), 3.42-3.66 (m, 1H, 5.24-5.46 (m, 1H), 7.27 (d, J=9.2 Hz, 1H), 7.38 (s, 1H), 7.53 (d, J=8.5 Hz, 1H), 7.82 (dd, J=8.5, 1.7 Hz, 1H), 8.05 (s, 1H), 8.11 (d, J=9.5 Hz, 1H) ppm. MS (DCI/NH3): 399 (M+H)+, 401 (M+H)+.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.15) as a solid (70 mg, yield, 35%)

Sources & evidence

ORD record
ord-6d6f0d245eab4ef0a0ff47e52e3f837c
Source dataset
uspto-grants-2010_02
Patent number
US07655657B2

Reaction notes

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