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

HRID 511075Notes

Reaction equation

HRID 511075 reaction equation
[Li+].[F:2][C:3]([F:22])([F:21])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]([O-:20])=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=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+: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>[N+:57]([C:60]1[CH:65]=[CH:64][C:63]([NH:66][CH:67]2[CH2:68][CH2:69][N:70]([C:18](=[O:20])[CH2:17][CH2:16][N:13]3[CH2:12][CH2:11][CH:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([F:21])([F:2])[F:22])=[CH:5][CH:6]=4)[CH2:15][CH2:14]3)[CH2:71][CH2:72]2)=[CH:62][C:61]=1[C:73]([F:76])([F:74])[F:75])([O-:59])=[O:58]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585768843-[4-(4-Trifluoromethyl-phenyl)-piperidin-1-yl]-propionic acid lithium saltHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product 1

HCID 585766551-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-3-[4-(4-trifluoromethyl-phenyl)-piperidin-1-yl]-propan-1-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-[4-(4-Trifluoromethyl-phenyl)-piperidin-1-yl]-propionic acid lithium salt (118 mg; 0.38 mmol, prepared in accordance with Example 13), diisopropylethyl amine (137 μL; 0.76 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (145 mg; 0.38 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (12 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 (4 mL) is added and the reaction is then stirred for 2 hours at room temperature. Following dilution with dichloromethane (50 mL), the organic layer is sequentially washed with water (15 mL), aq. sat. sodium hydrogen carbonate (15 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The desired product is finally obtained in pure form (103 mg; 0.18 mmol) following purification by preparative HPLC. The structure was confirmed using Protocol II-A. Calculated mass=572; observed mass=573; HPLC retention time=3.62 min.

Workup

  1. stirringthe reaction is then stirred for 2 hours at room temperature
  2. washthe organic layer is sequentially washed with water (15 mL), aq. sat. sodium hydrogen carbonate (15 mL)
  3. dry with materialis dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-715f74aa59f1465fa1b7dd4a3a8500a0
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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