Diisopropylethylamine → HCID 58577063, compound

HRID 511135Notes

Reaction equation

HRID 511135 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-])=[O:25])[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.[N+:65]([C:68]1[CH:73]=[CH:72][C:71]([NH:74][CH:75]2[CH2:80][CH2:79][NH:78][CH2:77][CH2:76]2)=[CH:70][C:69]=1[C:81]([F:84])([F:83])[F:82])([O-:67])=[O:66]>CN(C)C=O.ClCCl.O1CCCC1>[N+:65]([C:68]1[CH:73]=[CH:72][C:71]([NH:74][CH:75]2[CH2:76][CH2:77][N:78]([C:24](=[O:25])[CH2:23][CH2:22][N:19]3[CH2:20][CH2:21][N:16]([C:13]4[CH:14]=[CH:15][C:10]([O:9][CH2:8][C:7]5[CH:6]=[CH:5][C:4]([C:3]([F:2])([F:30])[F:29])=[CH:28][CH:27]=5)=[CH:11][CH:12]=4)[CH2:17][CH2:18]3)[CH2:79][CH2:80]2)=[CH:70][C:69]=1[C:81]([F:84])([F:82])[F:83])([O-:67])=[O:66]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58576292HCID 58576292, compoundHCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Product 1

HCID 58577063HCID 58577063, 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 (134 mg; 0.32 mmol, prepared in accordance with Example 13), diisopropylethyl amine (174 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-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride (114 mg; 0.30 mmol, prepared in accordance with Example 8) 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 (34 mg; 0.05 mmol). The structure was confirmed using Protocol II-A. Calculated mass=680; observed mass=680; HPLC retention time=3.84 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-273ad221a1674282b076855b8759fe8d
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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