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

HRID 37804Notes

Reaction equation

HRID 37804 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:18]3[NH:17][C:16]4[CH:19]5[CH2:25][CH2:24][N:22]([CH2:23][C:15]=4[C:14]=3[CH:13]=[CH:12][CH:11]=2)[CH2:21][CH2:20]5)=[CH:4][CH:3]=1>CO.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2]>[CH3:1][C:2]1[N:7]=[CH:6][C:5](/[CH:8]=[CH:9]\[C:10]2[C:18]3[NH:17][C:16]4[CH:19]5[CH2:25][CH2:24][N:22]([CH2:23][C:15]=4[C:14]=3[CH:13]=[CH:12][CH:11]=2)[CH2:21][CH2:20]5)=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 532507637-[(6-methylpyridin-3-yl)ethynyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Product 1

HCID 532514297-[(Z)-2-(6-methylpyridin-3-yl)vinyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 131709914Lindlars catalystCatalystHCID 887MethanolSolvent

Procedure

The product of Example 3 (100.9 mg, 0.308 mmol) was dissolved in methanol (5 mL). Lindlar catalyst (5% Pd on CaCO3 poisoned with lead, Aldrich, 9.8 mg) was added to the reaction mixture. The reaction flask was purged with nitrogen then purged with hydrogen, and the mixture was stirred under hydrogen (1 atm) at room temperature for 3 hours. The flask was purged with nitrogen and the reaction mixture was filtered. The filtrate was concentrated under vacuum, and the residue was 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 (300 MHz, methanol-d4) δ ppm 2.01-2.10 (m, 4H), 2.41 (s, 3H), 2.97-3.13 (m, 3H), 3.21-3.26 (m, 2H), 26 (s, 2H), 6.69 (d, J=12.2 Hz, 1H), 6.88-6.90 (m, 2H), 6.99 (d, J=11.9 Hz, 1H), 7.04 (d, J=8.1 Hz, 1H), 7.21-7.26 (m, 1H) 7.44 (dd, J=8.2, 2.0 Hz, 1H), 8.16 (d, J=2.4 Hz, 1H); MS (APCI) m/z 330 (M+H)+.

Workup

  1. customThe reaction flask was purged with nitrogen
  2. customthen purged with hydrogen
  3. customThe flask was purged with nitrogen
  4. filtrationthe reaction mixture was filtered
  5. concentrationThe filtrate was concentrated under vacuum
  6. customthe residue was 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)]

Sources & evidence

ORD record
ord-e5a2f8c0ebc8468fa4225b0de8237811
Source dataset
uspto-grants-2013_09
Patent number
US08524703B2

Reaction notes

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