Diisopropylethylamine → 3-[4-(4-Benzyloxy-phenyl)-piperazin-1-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one

HRID 511083Notes

Reaction equation

HRID 511083 reaction equation
[Li+].[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]([O-])=[O:25])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C)C(ON1C2C=CC=CC=2N=N1)=[N+](C)C.Cl.[N+:61]([C:64]1[CH:69]=[CH:68][C:67]([NH:70][CH:71]2[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]2)=[CH:66][C:65]=1[C:77]([F:80])([F:79])[F:78])([O-:63])=[O:62]>CN(C)C=O.ClCCl.O1CCCC1>[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]([N:74]3[CH2:75][CH2:76][CH:71]([NH:70][C:67]4[CH:68]=[CH:69][C:64]([N+:61]([O-:63])=[O:62])=[C:65]([C:77]([F:78])([F:79])[F:80])[CH:66]=4)[CH2:72][CH2:73]3)=[O:25])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585767383-[4-(4-Benzyloxy-phenyl)-piperazin-1-yl]-propionic acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product 1

HCID 469465663-[4-(4-Benzyloxy-phenyl)-piperazin-1-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-[4-(4-Benzyloxy-phenyl)-piperazin-1-yl]-propionic acid lithium salt (134 mg; 0.39 mmol, prepared in accordance with Example 22), diisopropylethyl amine (174 μL; 0.35 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (133 mg; 0.35 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (1.5 mL) and the resulting solution is stirred for 5 minutes. A solution of (4-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (114 mg; 0.35 mmol, prepared in accordance with Example 8) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 3 hours at room temperature. Following dilution with dichloromethane (10 mL), the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (5 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained is finally purified by preparative HPLC to deliver the desired product in pure form (61 mg; 0.10 mmol). The structure was confirmed using Protocol II-A. Calculated mass=612; observed mass=612; HPLC retention time=3.57 min.

Workup

  1. stirringthe reaction is then stirred for 3 hours at room temperature
  2. washthe organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (5 mL)
  3. dry with materialis dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. customis finally purified by preparative HPLC

Sources & evidence

ORD record
ord-61eb19c3e71e41f881364e90bf7153aa
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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