Reaktion #1755672

Reaktionsgleichung

thiophene-2-carboximidothioic acid methyl ester hydroiodide

compound 103

(S)-1-((1-Methylpyrrolidin-2-yl)methyl)-1H-indol-5-amine

→

compound 104

Ausbeute 62.6%

(S)—N-(1-((1-Methylpyrrolidin-2-yl)methyl)-1H-indol-5-yl)thiophene-2-carboximidamide

Ausbeute 62.6%

NH3

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigefitted with a magnetic stir bar
2. 2
   Sonstigewas evaporated
3. 3
   Sonstigethe residue was partitioned between H2O and ethyl acetate and 1M sodium hydroxide solution
4. 4
   workup.ADDITIONadded
5. 5
   SonstigeThe mixture was transferred to a separatory funnel
6. 6
   Sonstigethe organic layer collected
7. 7
   ExtraktionThe aqueous layer was further extracted with ethyl acetate
8. 8
   Waschenthe combined organic layers were washed with brine
9. 9
   Trocknendried over magnesium sulphate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    Sonstigethe residue purified via chromatography on silica gel (MeOH

Vorschrift

compound 103 (65 mg, 0.283 mmol) is charged to a small, argon purged flask fitted with a magnetic stir bar. Anhydrous ethanol (7 mL) and thiophene-2-carboximidothioic acid methyl ester hydroiodide (121.2 mg, 0.425 mmol) are added to the flask and the reaction was stirred under argon at ambient temperature for 17 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 (MeOH:CH2Cl2, 1:9 then 2M NH3 in MeOH:CH2Cl2, 5:95 to 1:9) to yield compound 104 (30 mg, 31.3%) as a yellow solid. 1H NMR (DMSO-d6) δ 1.47-1.76 (m, 4H), 2.16 (q, 1H, J=8.5 Hz), 2.25 (s, 3H), 2.50-2.59 (m, 1H), 2.92-3.02 (m, 1H), 3.97 (dd, 1H, J=14.1, 7.1 Hz), 4.23 (dd, 1H, J=14.0, 4.8 Hz), 6.23 (brs, 2H), 6.31 (d, 1H, J=3.0 Hz), 6.69 (d, 1H, J=8.3 Hz), 6.98 (s, 1H), 7.08-7.11 (m, 1H), 7.31 (d, 1H, J=3.0 Hz), 7.39 (d, 1H, J=8.6 Hz), 7.58 (d, 1H, J=5.2 Hz), 7.71 (d, 1H, J=3.7 Hz); ESI-MS (m/z, %): 339 (MH+, 100%); ESI-HRMS calculated for C19H23N4S (MH+): 339.1637, observed: 339.1653.

Quelle