1-(Quinuclidin-3-yl)-1H-indol-5-amine → HCID 178511913, compound

HRID 1668464Notes

Reaction equation

HRID 1668464 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([N:9]1[C:17]3[C:12](=[CH:13][C:14]([NH2:18])=[CH:15][CH:16]=3)[CH:11]=[CH:10]1)[CH2:2]2.I.CS[C:22]([C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)=[NH:23]>C(O)C>[N:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[CH:3]([N:9]1[C:17]3[C:12](=[CH:13][C:14]([NH:18][C:22]([C:24]4[S:25][CH:26]=[CH:27][CH:28]=4)=[NH:23])=[CH:15][CH:16]=3)[CH:11]=[CH:10]1)[CH2:2]2

Participants

4

Reactant 2

HCID 590046571-(Quinuclidin-3-yl)-1H-indol-5-amineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178511913HCID 178511913, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Compound 70 (60 mg, 0.249 mmol) is charged to a small, argon purged flask fitted with a magnetic stir bar. Anhydrous ethanol (5 mL) and thiophene-2-carboximidothioic acid methyl ester hydroiodide (124 mg, 0.435 mmol) are added to the flask and the reaction was stirred under argon at ambient temperature for 18 hours, at which time the solvent was evaporated and the residue was partitioned between H2O and ethyl acetate and 1M sodium hydroxide solution added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95 to 7.5:92.5) then a second time on silica gel (methanol:CH2Cl2, 1:9 to 2 M NH3 in methanol:CH2Cl2, 1:9) to yield a yellow solid, 71 (30 mg, 34.4%). 1H NMR (DMSO-d6) δ 1.27-1.53 (2×m, 2H), 1.60-1.69 (m, 1H), 1.79-1.96 (2×m, 2H), 2.69-2.87 (m, 3H), 3.03-3.13 (m, 1H), 3.19-3.30 (m, 1H), 3.34-3.44 (m, 1H), 4.57-4.68 (m, 1H), 6.28 (brs, 2H), 6.39 (d, 1H, J=3.1 Hz), 6.70 (dd, 1H, J=8.4, 1.6 Hz), 7.00 (d, 1H, J=1.2 Hz), 7.09 (dd, 1H, J=4.9, 3.9 Hz), 7.39 (d, 1H, J=8.6 Hz), 7.59 (d, 1H, J=5.1 Hz), 7.67 (d, 1H, J=3.2 Hz), 7.71 (d, 1H, J=3.5 Hz); ESI-MS (m/z, %): 351 (M+1, 60%), 176 (M++doubly charged, 100%); ESI-HRMS calculated for C20H23N4S (MH+): 351.1637, observed: 351.1639.

Workup

  1. customfitted with a magnetic stir bar
  2. customwas evaporated
  3. customthe residue was partitioned between H2O and ethyl acetate and 1M sodium hydroxide solution
  4. additionadded
  5. customThe mixture was transferred to a separatory funnel
  6. customthe organic layer collected
  7. extractionThe aqueous layer was further extracted with ethyl acetate
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customthe residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95 to 7.5:92.5)

Sources & evidence

ORD record
ord-650e7f577d8b4fd5a4a20578787ca04b
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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