Reaktion #2263355

Reaktionsgleichung

10-methyl-1,3,4,5,6,7-hexahydro-2,6-methanoazocino[4,3-b]indole

sodium

2-methyl-5-vinylpyridine

hydroquinone

→

title compound

10-methyl-7-[2-(6-methylpyridin-3-yl)ethyl]-1,3,4,5,6,7-hexahydro-2,6-methanoazocino[4,3-b]indole

Lösungsmittel

dimethyl sulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction was purged with nitrogen for 15 minutes
2. 2
   TemperaturAfter cooling
3. 3
   Sonstigethe reaction was partitioned between 1 M K2CO3 (35 mL) and chloroform (3×35 mL)
4. 4
   WaschenThe combined organic layers were washed with brine (35 mL)
5. 5
   Trocknendried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   workup.ADDITIONMethanol (10 mL) was added to the residue
9. 9
   Filtrationthe resulting suspension was filtered through diatomaceous earth
10. 10
    Sonstigepurified by preparative HPLC (Phenomenex® Luna® Combi-HTS™ C8(2) 5 μm 100 Å AXIA™ 30×75 mm column, gradient of 10-100% acetonitrile in 0.1% trifluoroacetic acid, flow rate 50 mL/minute)

Vorschrift

A solution of 10-methyl-1,3,4,5,6,7-hexahydro-2,6-methanoazocino[4,3-b]indole (173.8 mg, 0.768 mmol; Example 201) in dimethyl sulfoxide (3 mL) was treated with sodium (30% dispersion in paraffin; 87.7 mg, 1.144 mmol; Aldrich), 2-methyl-5-vinylpyridine (204.6 mg, 1.717 mmol; prepared as described in International Publication No. WO 2001017968) and hydroquinone (28.6 mg, 0.260 mmol; Aldrich). The reaction was purged with nitrogen for 15 minutes, then heated to 100° C. for 17 hours. After cooling, the reaction was partitioned between 1 M K2CO3 (35 mL) and chloroform (3×35 mL). The combined organic layers were washed with brine (35 mL), dried over sodium sulfate, filtered and concentrated. Methanol (10 mL) was added to the residue and the resulting suspension was filtered through diatomaceous earth, then purified by preparative HPLC (Phenomenex® Luna® Combi-HTS™ C8(2) 5 μm 100 Å AXIA™ 30×75 mm column, gradient of 10-100% acetonitrile in 0.1% trifluoroacetic acid, flow rate 50 mL/minute) to afford the title compound as the bis trifluoroacetic acid salt: 1H NMR (300 MHz, methanol-d4) δ ppm 1.54-1.78 (m, 3H), 1.95-2.05 (m, 1H), 2.41 (s, 3H), 2.67 (s, 3H), 3.42-3.55 (m, 4H), 3.68-3.72 (m, 1H), 4.34-4.41 (m, 1H), 4.48-4.57 (m, 2H), 7.01 (d, J=8.3 Hz, 1H), 7.17 (d, J=8.3 Hz, 1H), 7.27 (s, 1H), 7.69 (d, J=8.3 Hz, 1H), 8.03 (dd, J=8.3, 2.0 Hz, 1H), 8.22 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 347 (M+H)+.

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