Diisopropylethylamine → 4-[4-(4-Tert-butyl-phenyl)-piperazin-1-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-butan-1-one

HRID 511134Notes

Reaction equation

HRID 511134 reaction equation
[Li+].[C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][C:21]([O-:23])=O)[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3].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+:58]([C:61]1[CH:66]=[CH:65][C:64]([NH:67][CH:68]2[CH2:73][CH2:72][NH:71][CH2:70][CH2:69]2)=[CH:63][C:62]=1[C:74]([F:77])([F:76])[F:75])([O-:60])=[O:59]>CN(C)C=O.ClCCl.O1CCCC1>[C:2]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][C:21]([N:71]3[CH2:72][CH2:73][CH:68]([NH:67][C:64]4[CH:65]=[CH:66][C:61]([N+:58]([O-:60])=[O:59])=[C:62]([C:74]([F:75])([F:76])[F:77])[CH:63]=4)[CH2:69][CH2:70]3)=[O:23])[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585763684-[4-(4-Tert-butylphenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product 1

HCID 585760744-[4-(4-Tert-butyl-phenyl)-piperazin-1-yl]-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-butan-1-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-[4-(4-tert-Butyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (15 mg; 0.05 mmol, prepared in accordance with Example 167), diisopropylethyl amine (25 μL; 0.15 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 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 (16 mg; 0.05 mmol, prepared in accordance with Example 8) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 2 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 (3×5 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 (16 mg; 0.03 mmol). The structure was confirmed using Protocol I-C. Calculated mass=576; observed mass=576; HPLC retention time=3.16 min.

Workup

  1. stirringthe reaction is then stirred for 2 hours at room temperature
  2. washthe organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (3×5 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-b322ddc804044c8daa89980c045d3908
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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