Piperidine → HCID 86762016, compound

HRID 1895932Notes

Reaction equation

HRID 1895932 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[S:7](Cl)(Cl)(=[O:9])=[O:8].Cl.[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][O:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[O:22])=[CH:16][CH:15]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][O:24][CH:25]2[CH2:30][CH2:29][N:28]([S:7]([N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)(=[O:9])=[O:8])[CH2:27][CH2:26]2)=[O:22])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 86652736HCID 86652736, compound

Product 1

HCID 86762016HCID 86762016, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of piperidine (300 mg, 3.5 mmol) in CH2Cl2 (10 ml) was added at 0° C. over 30 minutes to a suspension of sulfuryl dichloride (952 mg, 7.0 mmol) in CH2Cl2 (35 ml) and the whole was stirred at room temperature for 17 hours. The resulting solid was filtered off and the filtrate was concentrated in vacuo. The residue was dissolved in CH2Cl2 (15 ml), 1-(4-fluorophenyl)-3-(piperidin-4-yloxy)urea hydrochloride (130 mg, 0.45 mmol) and N,N-diisopropylethylamine (174 mg, 1.35 mmol) was added, and the whole was stirred at 50° C. for 24 hours. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (50 ml), washed with H2O (20 ml×2), brine (20 ml×2), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/petroleum ether: 50/50) to give 1-(4-fluorophenyl)-3-(1-(piperidin-1-ylsulfonyl)piperidin-4-yloxy)urea (90 mg, 50%) as a white solid: LCMS: 401 [M+1]+. 1H NMR (DMSO-d6) δ: 1.48 (s, 6H), 1.7 (m, 2H), 1.89 (m, 2H), 2.98 (m, 2H), 3.1 (m, 4H), 3.4 (m, 2H), 3.87 (m, 1H), 7.08 (t, 2H), 7.86 (m, 2H), 8.65 (s, 1H), 9.42 (s, 1H).

Workup

  1. filtrationThe resulting solid was filtered off
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (15 ml)
  4. stirringthe whole was stirred at 50° C. for 24 hours
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. additionthe residue was diluted with ethyl acetate (50 ml)
  7. washwashed with H2O (20 ml×2), brine (20 ml×2)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (ethyl acetate/petroleum ether: 50/50)

Sources & evidence

ORD record
ord-680cdd3928644202a020ddd0220acdf3
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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