Diisopropylethylamine → HCID 46946968, compound

HRID 511120Notes

Reaction equation

HRID 511120 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.[CH3:58][C:59]1[C:64]([N+:65]([O-:67])=[O:66])=[CH:63][N:62]=[C:61]([NH:68][CH:69]2[CH2:74][CH2:73][NH:72][CH2:71][CH2:70]2)[CH:60]=1>CN(C)C=O.ClCCl.O1CCCC1>[CH3:58][C:59]1[C:64]([N+:65]([O-:67])=[O:66])=[CH:63][N:62]=[C:61]([NH:68][CH:69]2[CH2:74][CH2:73][N:72]([C:19](=[O:20])[CH2:18][CH2:17][CH2:16][N:13]3[CH2:14][CH2:15][N:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([F:23])([F:2])[F:22])=[CH:5][CH:6]=4)[CH2:11][CH2:12]3)[CH2:71][CH2:70]2)[CH:60]=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 66671832HCID 66671832, compound

Product 1

HCID 46946968HCID 46946968, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (122 mg; 0.39 mmol, prepared in accordance with Example 3), diisopropylethyl amine (175 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 of (4-methyl-5-nitro-pyridin-2-yl)-piperidin-4-yl-amine hydrochloride (95 mg; 0.35 mmol, prepared in accordance with Example 70) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 3 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 (33 mg; 0.06 mmol). The structure was confirmed using Protocol II-A. Calculated mass=535; observed mass=535; HPLC retention time=3.29 min.

Workup

  1. stirringthe reaction is then stirred for 3 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-f857fc20b066490aaceff8c78a25a535
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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