Diisopropylethylamine → HCID 46946365, compound

HRID 511145Notes

Reaction equation

HRID 511145 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:72]=[CH:71][C:68]([C:69]#[N:70])=[C:67]([C:73]([F:76])([F:75])[F:74])[CH:66]=2)[CH2:60][CH2:59]1>CN(C)C=O.ClCCl.O1CCCC1>[F:76][C:73]([F:74])([F:75])[C:67]1[CH:66]=[C:65]([NH:64][CH:61]2[CH2:62][CH2:63][N:58]([C:19](=[O:20])[CH2:18][CH2:17][CH2:16][N:13]3[CH2:14][CH2:15][N:10]([C:7]4[CH:6]=[CH:5][C:4]([C:3]([F:22])([F:23])[F:2])=[CH:9][CH:8]=4)[CH2:11][CH2:12]3)[CH2:59][CH2:60]2)[CH:72]=[CH:71][C:68]=1[C:69]#[N:70]

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 66671763HCID 66671763, compound

Product 1

HCID 46946365HCID 46946365, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (16 mg; 0.05 mmol, prepared in, prepared in accordance with Example 3), 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-(piperidin-4-ylamino)-2-trifluoromethyl-benzonitrile hydrochloride (15 mg; 0.05 mmol) 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 (23 mg; 0.04 mmol). The structure was confirmed using Protocol I-B. Calculated mass=568; observed mass=568; HPLC retention time=5.10 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-c73f2f5bd9e540688a70dd9ed2308a8a
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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