Acetonitrile → 9-bromo-3,4,5,10-tetrahydro-1H-2,5-ethanoazepino[3,4-b]indole

Reaction equation

[C:1](#[N:3])[CH3:2].F[C:5](F)(F)[C:6](O)=O.[Br:11][C:12]1[C:20]2[NH:19][C:18]3[CH:21]4CCN([CH2:25][C:17]=3[C:16]=2[CH:15]=[CH:14][CH:13]=1)CC4>O>[Br:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:20]=1[NH:19][C:18]1[CH2:21][N:3]3[CH2:6][CH2:5][CH:25]([C:17]2=1)[CH2:2][CH2:1]3

Participants

Procedure

Crude reaction mixture was obtained as described in Example 1B. Analytical HPLC analysis [Phenomenex® Luna® Combi-HTS C8 (2) 5 μm 100 Å (2.1×30 mm), a gradient of 10-100% acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) at a flow rate of 2.0 mL/minute over 3 minutes (0-0.1 minute 10% A, 0.1-2.6 minutes 10-100% A)] identified the product of Example 1B as the major product (retention time 1.77 minutes) and the title compound as the minor product (retention time 1.95 minutes). The crude reaction mixture was dissolved in dimethyl sulfoxide and then was purified by reverse-phase HPLC (Waters XBridge™ C18 5 μm OBD 30×100 mm column, flow rate 40 mL/minute, 20-99% gradient of methanol in water with 0.1% trifluoroacetic acid over 20 minutes) to afford a major fraction containing the product of Example 1B and a minor fraction containing the title compound. The fractions containing the title compound were combined and partitioned between CHCl3/2-propanol (4:1, 2×200 mL) and 1.0 M sodium carbonate (200 mL). The combined organic extracts were dried (sodium sulfate) and concentrated under vacuum to afford the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 1.92-2.13 (m, 4 H), 2.99-3.10 (m, 2 H), 3.19-3.28 (m, 3 H), 4.28 (s, 2 H), 6.88 (t, J=7.8 Hz, 1 H), 7.17 (dd, J=7.6, 0.6 Hz, 1 H), 7.38 (d, J=7.9 Hz, 1 H); MS (APCI) m/z 291/293 (M+H)+.