1-(Quinuclidin-3-yl)-1H-indol-5-amine → HCID 178511913、化合物

HRID 1668464ノート

反応式

HRID 1668464 の反応式
[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

参加物

4

反応物 2

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

生成物 1

HCID 178511913HCID 178511913、化合物収率 34.4%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-650e7f577d8b4fd5a4a20578787ca04b
出典データセット
uspto-grants-2011_08
特許番号
US07989447B2

反応ノート

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