Diisopropylethylamine → HCID 58576847, compound

HRID 511093Notes

Reaction equation

HRID 511093 reaction equation
[Li+].[F:2][C:3]([F:30])([F:29])[C:4]1[CH:28]=[CH:27][C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]([O-:26])=O)[CH2:18][CH2:17]3)=[CH:12][CH: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.[CH3:65][O:66][C:67]1[CH:68]=[C:69]([NH:76][CH:77]2[CH2:82][CH2:81][NH:80][CH2:79][CH2:78]2)[CH:70]=[CH:71][C:72]=1[N+:73]([O-:75])=[O:74]>CN(C)C=O.ClCCl.O1CCCC1>[CH3:65][O:66][C:67]1[CH:68]=[C:69]([NH:76][CH:77]2[CH2:82][CH2:81][N:80]([C:24](=[O:26])[CH2:23][CH2:22][N:19]3[CH2:18][CH2:17][N:16]([C:13]4[CH:14]=[CH:15][C:10]([O:9][CH2:8][C:7]5[CH:27]=[CH:28][C:4]([C:3]([F:2])([F:29])[F:30])=[CH:5][CH:6]=5)=[CH:11][CH:12]=4)[CH2:21][CH2:20]3)[CH2:79][CH2:78]2)[CH:70]=[CH:71][C:72]=1[N+:73]([O-:75])=[O:74]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58576292HCID 58576292, compoundHCID 66671736HCID 66671736, compound

Product 1

HCID 58576847HCID 58576847, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-{4-[4-(4-Trifluoromethyl-benzyloxy)-phenyl]-piperazin-1-yl}-propionic acid lithium salt (160 mg; 0.39 mmol, prepared in accordance with Example 37), diisopropylethyl amine (134 μL; 0.77 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (127 mg; 0.39 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 (3-methoxy-4-nitro-phenyl)-piperidin-4-yl-amine hydrochloride (100 mg; 0.35 mmol, prepared in accordance with Example 39) in dimethylformamide (0.5 mL) is added and the reaction is 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 (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 (29.5 mg; 0.05 mmol). The structure was confirmed using Protocol II-A. Calculated mass=642; observed mass=642; HPLC retention time=3.68 min.

Workup

  1. stirringthe reaction is stirred for 3 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-8974facb6761426e9e0b370a957b0676
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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