Potassium Iodide → HCID 22484039, compound

HRID 1178244Notes

Reaction equation

HRID 1178244 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[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.O1CCCC1.[I-].[K+].Cl[CH2:25][CH2:26][CH2:27][C:28]([N:30]1[CH2:39][CH2:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH2:31]1)=[O:29]>CC(=O)CC.C(OCC)(=O)C.C(N(CC)CC)C.CO>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH2:25][CH2:26][CH2:27][C:28]([N:30]2[CH2:39][CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31]2)=[O:29])[CH2:13][CH2:12]1

Participants

9

Reactant 4

HCID 4875Potassium IodideHCID 8028TetrahydrofuranHCID 4993909HCID 4993909, compoundHCID 117699295-fluoro-3-(piperidin-4-yl)-1H-indole

Product 1

HCID 22484039HCID 22484039, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6569Methyl Ethyl KetoneSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-fluoro-3-(piperidin-4-yl)-1H-indole (3.0 g), butanone (200 mL), tetrahydrofuran (200 mL), methanol (30 mL), potassium iodide (11.4 g) and triethylamine (7.6 mL) was heated until reflux temperature followed by the addition of a solution of 4-chloro-1-(3,4-dihydro-1H-isoquinolin-2-yl)butan-1-one (14.6 g) in butanone (50 mL). The mixture was boiled under reflux for 2 h, filtered hot and concentrated in vacuo. The residue was purified by flash chromatography on silicagel (eluent: ethyl acetate/ethanol/triethylamine 100:5:5) to give the crude product. The title compound was isolated as the free base from ethyl acetate as a white crystalline compound (0.9 g). Mp 146-148° C. 1H NMR (DMSO-d6): 1.55-1.70 (m, 2H); 1.70-1.80 (m, 2H); 1.85-1.95 (m, 2H); 2.00 (q, 2H); 2.30 (q, 2H); 2.35-2.45 (m, 2H); 2.60-2.70 (m, 1H); 2.75 (t, 0.8H); 2.80-3.00 (m, 3.2H); 3.65 (t, 2H); 4.60 (s, 1.2H); 4.70 (s, 0.8H); 6.85-6.95 (m, 1H); 7.10-7.20 (m, 5H); 7.25 (d, 1H); 7.30-7.35 (m, 1H); 10.85 (s, 1H). MS m/z: 420 (MH+), 202.

Workup

  1. temperaturewas heated
  2. temperatureuntil reflux temperature
  3. temperatureunder reflux for 2 h
  4. filtrationfiltered hot
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silicagel (eluent: ethyl acetate/ethanol/triethylamine 100:5:5)
  7. customto give the crude product

Sources & evidence

ORD record
ord-a198d408f8204990b84933bea1209d76
Source dataset
uspto-grants-2007_10
Patent number
US07276508B2

Reaction notes

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