Reaktion #2494369

Reaktionsgleichung

Triethylamine

5-ethynyl-2-methylpyridine

product

6-bromo-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

→

title compound

2-methyl-6-[(6-methylpyridin-3-yl)ethynyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was purged with a nitrogen stream for 2 minutes
2. 2
   workup.WAITat 35° C. for 18 hours in a sealed tube
3. 3
   FiltrationThe mixture was filtered through a glass microfiber frit
4. 4
   Waschenrinsed with CH3OH (3 mL)
5. 5
   Sonstigepurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 50-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]
6. 6
   workup.ADDITIONFractions containing the product
7. 7
   Einengenwere concentrated under vacuum
8. 8
   Sonstigethe residue was further purified by flash chromatography (silica gel, eluted with CHCl3—CH3OH-14.8 M aqueous NH4OH (90:10:1))

Vorschrift

Triethylamine (1.5 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (12.3 mg, 0.024 mmol; Aldrich), 5-ethynyl-2-methylpyridine (85 mg, 0.72 mmol; International Publication No. WO2005090333), CuI (4.6 mg, 0.024 mmol; Aldrich) and the product of Example 1A (128 mg, 0.48 mmol) in anhydrous tetrahydrofuran (1.5 mL). The mixture was purged with a nitrogen stream for 2 minutes, then stirred under nitrogen at 75° C. for 2 hours and then at 35° C. for 18 hours in a sealed tube. The mixture was filtered through a glass microfiber frit, rinsed with CH3OH (3 mL) and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 50-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]. Fractions containing the product were concentrated under vacuum and the residue was further purified by flash chromatography (silica gel, eluted with CHCl3—CH3OH-14.8 M aqueous NH4OH (90:10:1)) to provide the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 2.55 (s, 3H), 2.56 (s, 3H), 2.89 (t, J=5.8 Hz, 2H), 2.98 (t, J=5.5 Hz, 2H), 3.69 (s, 2H), 6.97-7.04 (m, 1H), 7.25 (dd, J=7.3, 0.9 Hz, 1H), 7.33 (d, J=7.9 Hz, 1H), 7.41 (dd, J=7.8, 1.1 Hz, 1H), 7.94 (dd, J=7.9, 2.1 Hz, 1H), 8.68 (d, J=1.8 Hz, 1H); MS (DCI) m/z 302 (M+H)+.

Quelle