Hydrazine hydrate (1:1) → HCID 86652739, compound

HRID 1895942Notes

Reaction equation

HRID 1895942 reaction equation
O.NN.[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[N:12]2[CH2:17][CH2:16][CH:15]([O:18][N:19]3[C:27](=[O:28])C4C(=CC=CC=4)C3=O)[CH2:14][CH2:13]2)=[CH:7][CH:6]=1.[F:37][C:38]1[CH:43]=[CH:42][C:41]([N:44]=C=O)=[CH:40][CH:39]=1>C(Cl)Cl>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH:11]([C:8]2[CH:9]=[CH:10][C:5]([F:4])=[CH:6][CH:7]=2)[N:12]2[CH2:17][CH2:16][CH:15]([O:18][NH:19][C:27]([NH:44][C:41]3[CH:42]=[CH:43][C:38]([F:37])=[CH:39][CH:40]=3)=[O:28])[CH2:14][CH2:13]2)=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 709554-Fluorophenyl isocyanateHCID 67118425HCID 67118425, compound

Product 1

HCID 86652739HCID 86652739, compoundYield 131.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Hydrazine monohydrate (0.059 ml, 1.2 mmol) was added to a solution of 2-(1-(bis(4-fluorophenyl)methyl)piperidin-4-yloxy)isoindoline-1,3-dione (193 mg, 0.406 mmol) in CH2Cl2 (5 ml) and stirred at room temperature for 15 hours. The resulting solid was filtered off and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (5 ml), 4-fluorophenyl isocyanate (0.023 ml, 0.20 mmol) was added and the whole was stirred at room temperature for 15 hours. The reaction mixture was concentrated in vacuo, the residue was purified by column chromatography (ethyl acetate/hexane: 25/75 to 45/55) and the resulting solid was recrystallized from ethyl acetate/hexane to give 1-(1-(bis(4-fluorophenyl)methyl)piperidin-4-yloxy)-3-(4-fluorophenyl)urea (120 mg, 65%) as a white solid: LCMS: 456 [M+1]+. 1H NMR (DMSO-d6) δ: 1.68 (m, 2H), 1.90-2.02 (m, 4H), 2.62 (m, 2H), 3.70 (m, 1H), 4.40 (s, 1H), 7.10 (m, 6H), 7.43 (m, 4H), 7.55 (m, 2H), 8.61 (s, 1H), 9.38 (s, 1H).

Workup

  1. filtrationThe resulting solid was filtered off
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in tetrahydrofuran (5 ml)
  4. stirringthe whole was stirred at room temperature for 15 hours
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe residue was purified by column chromatography (ethyl acetate/hexane: 25/75 to 45/55)
  7. customthe resulting solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-cf1e1653818b418ebc19d88ae43fa140
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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