HCID 67545265, compound → HCID 67544033, compound

HRID 2176130Notes

Reaction equation

HRID 2176130 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=1)[C:6]1[CH2:23][CH:24]3[NH:29][CH:28]([C:5]2=1)[CH2:27][CH2:26][CH2:25]3>[Pd].C(O)C>[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:21])([F:20])[F:22])[CH:14]=1)[C:6]1[CH2:23][C@H:24]3[NH:29][C@@H:28]([C:5]2=1)[CH2:27][CH2:26][CH2:25]3

Participants

4

Reactant 1

HCID 67545265HCID 67545265, compound

Product 1

HCID 67544033HCID 67544033, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

In a 100 mL round-bottomed flask were combined 2-methyl-5-{(E)-2-[3-(trifluoromethyl)phenyl]vinyl}-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole (300 mg, 0.757 mmol; Example 134), 10% palladium on carbon (35 mg; Aldrich) in ethanol (30 mL). The reaction mixture was heated to 40° C. under a hydrogen balloon atmosphere for 16 hours, then cooled to room temperature. The catalyst and solvent were removed, and the residue was purified by reverse-phase HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1% trifluoroacetic acid) over 15 minutes] to afford the title compound as a racemic mixture. This material was purified further by preparative chiral supercritical fluid chromatography (ChiralPak® OD-H 5 μm column, 21×250 mm, 35° C., 10-50% gradient of CH3OH—CO2 containing 0.1% diethylamine, 20 minutes) to afford the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 0.97-1.17 (m, 1H), 1.22-1.42 (m, 2H), 1.61 (dd, J=13, 2 Hz, 1H), 1.74-1.95 (m, 2H), 2.06 (d, J=17 Hz, 1H), 2.40 (s, 3H), 2.87 (dd, J=17, 7 Hz, 1H), 3.10-3.23 (m, 2H), 3.44 (t, J=6 Hz, 1H), 4.25-4.44 (m, 3H), 6.93 (d, J=8 Hz, 1H), 7.13 (s, 1H), 7.17-7.23 (m, 2H), 7.29 (s, 1H), 7.35 (t, J=8 Hz, 1H), 7.42-7.48 (m, 1H); MS (DCI/NH3) m/z 399 (M+H)+.

Workup

  1. customIn a 100 mL round-bottomed flask were combined
  2. temperaturecooled to room temperature
  3. customThe catalyst and solvent were removed
  4. customthe residue was purified by reverse-phase HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1% trifluoroacetic acid) over 15 minutes]

Sources & evidence

ORD record
ord-ee673a44a4534698b55753fc9c4377ad
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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