Hydrochloric Acid → HCID 10135065, compound

HRID 2296742Notes

Reaction equation

HRID 2296742 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.Cl[CH2:19][CH2:20][O:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH:24]=[CH:25][NH:26]2.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl>C(#N)C.C(OCC)(=O)C.CCOCC>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH:12]1[CH2:17][CH2:16][N:15]([CH2:19][CH2:20][O:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:23]=2[CH:24]=[CH:25][NH:26]3)[CH2:14][CH2:13]1

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 106317214-(2-chloroethoxy)-1H-indoleHCID 112877165-fluoro-3-[(4-piperidinyl)methyl]-1H-indole

Product 1

HCID 10135065HCID 10135065, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 5-fluoro-3-[(4-piperidinyl)methyl]-1H-indole (0.84 g, 3.6 mmol) in acetonitrile (50 mL) was added 4-(2-chloroethoxy)-1H-indole (0.59 g, 3.6 mmol), potassium carbonate (0.48 g) followed by addition of potassium iodide (0.60 g) at room temperature. The reaction mixture was heated to reflux for 5 h and cooled. The reaction mixture was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (methylene chloride/methanol, 95/5) to 0.45 g (38%) of a white foam. The free base (0.23 g, 0.59 mmol) was dissolved in ethyl acetate, and precipitated with one equivalent of HCl in ether to give the title compound (0.16 g, 62%) as monohydrochloride, 1.0 hydrate: mp 215° C. (dec.); 1H NMR (DMSO, 400 MHz), 1.52-1.59 (m, 2H), 1.81-1.84 (m, 3H), 2.61 (d, 2H), 3.02-3.08 (m, 2H), 3.25-3.30 (m, 6H), 4.46 (t, 2H), 6.44-7.33 (m, 9H), 10.25 (br s, 1H), 10.98 (br s, 1H), 11.14 (br s, 1H); MS (FAB) m/z 392 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 5 h
  3. temperaturecooled
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel column chromatography (methylene chloride/methanol, 95/5) to 0.45 g (38%) of a white foam

Sources & evidence

ORD record
ord-c0a2c71369a3400dab95584223025def
Source dataset
uspto-grants-2002_12
Patent number
US06489342B2

Reaction notes

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