Diisopropylethylamine → 3-(1-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyryl}-piperidin-4-ylamino)-benzonitrile

HRID 511069Notes

Reaction equation

HRID 511069 reaction equation
[Li+].[F:2][C:3]([F:23])([F:22])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][C:19]([O-])=[O:20])[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.[NH:58]1[CH2:63][CH2:62][CH:61]([NH:64][C:65]2[CH:66]=[C:67]([CH:70]=[CH:71][CH:72]=2)[C:68]#[N:69])[CH2:60][CH2:59]1>CN(C)C=O.ClCCl.O1CCCC1>[F:2][C:3]([F:23])([F:22])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][C:19]([N:58]3[CH2:59][CH2:60][CH:61]([NH:64][C:65]4[CH:66]=[C:67]([CH:70]=[CH:71][CH:72]=4)[C:68]#[N:69])[CH2:62][CH2:63]3)=[O:20])[CH2:14][CH2:15]2)=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585760704-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 666720093-(Piperidin-4-ylamino)-benzonitrile hydrochloride

Product 1

HCID 469463673-(1-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyryl}-piperidin-4-ylamino)-benzonitrile

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (120 mg; 0.37 mmol, prepared in accordance with Example 3), diisopropylethyl amine (150 μL; 0.85 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (129 mg; 0.34 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (2.5 mL) and the resulting solution is stirred for 5 minutes. A solution 3-(piperidin-4-ylamino)-benzonitrile hydrochloride (80 mg; 0.34 mmol, prepared in accordance with Example 6) in dimethylformamide (850 μL) is added and the reaction is then stirred for 60 minutes 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 (67 mg; 0.14 mmol). The structure was confirmed using Protocol I-B. Calculated mass=500; observed mass=500; HPLC retention time=4.40 min.

Workup

  1. stirringthe reaction is then stirred for 60 minutes 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-d3e612ee0c6742c0a8a6bd44c92edbbc
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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