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

HRID 511090Notes

Reaction equation

HRID 511090 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][C:20]([O-:22])=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+:57]([C:60]1[CH:65]=[CH:64][C:63]([NH:66][CH:67]2[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]2)=[CH:62][C:61]=1[C:73]([F:76])([F:75])[F:74])([O-:59])=[O:58]>CN(C)C=O.ClCCl.O1CCCC1>[C:2]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C:20]([N:70]3[CH2:71][CH2:72][CH:67]([NH:66][C:63]4[CH:64]=[CH:65][C:60]([N+:57]([O-:59])=[O:58])=[C:61]([C:73]([F:74])([F:75])[F:76])[CH:62]=4)[CH2:68][CH2:69]3)=[O:22])[CH2:14][CH2:13]2)=[CH:10][CH:11]=1)([CH3:4])([CH3:3])[CH3:5]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585763193-[4-(4-Tert-butyl-phenyl)-piperazin-1-yl]-propionic acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product 1

HCID 585765553-[4-(4-Tert-butyl-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-tert-Butyl-phenyl)-piperazin-1-yl]-propionic acid lithium salt (114 mg; 0.39 mmol, prepared in accordance with Example 34), diisopropylethyl amine (174 μL; 1.0 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 (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 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 (2×5 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 (18 mg; 0.05 mmol). The structure was confirmed using Protocol II-F. Calculated mass=562; observed mass=563; HPLC retention time=12.14 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 (2×5 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-1cf162e904ad4370b395cae90835b41e
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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