Triethylamine → 7-[(6-methylpyridin-3-yl)ethynyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

HRID 37788

Reaction equation

C(N(CC)CC)C.[C:8]([C:10]1[CH:11]=[CH:12][C:13]([CH3:16])=[N:14][CH:15]=1)#[CH:9].Br[C:18]1[C:26]2[NH:25][C:24]3[CH:27]4[CH2:33][CH2:32][N:30]([CH2:31][C:23]=3[C:22]=2[CH:21]=[CH:20][CH:19]=1)[CH2:29][CH2:28]4>O1CCCC1.C(P([Pd]P(C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C)(C)C.[Cu]I>[CH3:16][C:13]1[N:14]=[CH:15][C:10]([C:8]#[C:9][C:18]2[C:26]3[NH:25][C:24]4[CH:27]5[CH2:33][CH2:32][N:30]([CH2:31][C:23]=4[C:22]=3[CH:21]=[CH:20][CH:19]=2)[CH2:29][CH2:28]5)=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Triethylamine (2 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (8.8 mg, 0.017 mmol; Aldrich), 5-ethynyl-2-methylpyridine (60 mg, 0.52 mmol; International Publication No. WO2005090333), CuI (3.3 mg, 0.017 mmol; Aldrich) and the product of Example 1B (100 mg, 0.34 mmol) in anhydrous tetrahydrofuran (2 mL). The mixture was purged with a nitrogen stream for 2 minutes, then stirred under nitrogen at 100° C. for 5 hours in a sealed tube. The mixture was cooled to ambient temperature and concentrated under vacuum. The residue was taken up in dimethyl sulfoxide (5 mL), filtered through a glass microfiber frit and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (500 MHz, methanol-d4 ) δ ppm 2.05-2.16 (m, 4 H), 2.56 (s, 3 H), 3.02-3.12 (m, 2 H), 3.17-3.21 (m, 1 H), 3.21-3.29 (m, 2 H), 4.24 (s, 2 H), 7.00 (t, J=7.6 Hz, 1 H), 7.24 (dd, J=7.3, 0.9 Hz, 1 H), 7.34 (d, J=7.9 Hz, 1 H), 7.36 (dd, J=7.9, 0.9 Hz, 1 H), 7.94 (dd, J=8.1, 2.3 Hz, 1 H), 8.68 (d, J=1.8 Hz, 1H); MS (APCI) m/z 328 (M+H)+.

Workup

customThe mixture was purged with a nitrogen stream for 2 minutes
temperatureThe mixture was cooled to ambient temperature
concentrationconcentrated under vacuum
filtrationfiltered through a glass microfiber frit
custompurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record: ord-632cec0b95cc4311834cef9b6ca8b826
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524703B2

Linked notes

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