Triethylamine → 2-Methyl-1-(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]piperidin-1-yl)-3-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]propan-1-one

HRID 1772256Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1772256
[CH3:1][CH:2]([CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:19]=3)[N:14]=2)[CH2:9][CH2:8]1)[C:3]([OH:5])=O.CCN=C=NCCCN(C)C.Cl.N1(O)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[N+:56]([C:59]1[CH:64]=[CH:63][C:62]([NH:65][CH:66]2[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]2)=[CH:61][C:60]=1[C:72]([F:75])([F:74])[F:73])([O-:58])=[O:57]>ClCCl>[CH3:1][CH:2]([CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:23]([F:25])([F:24])[F:26])[CH:19]=3)[N:14]=2)[CH2:9][CH2:8]1)[C:3]([N:69]1[CH2:70][CH2:71][CH:66]([NH:65][C:62]2[CH:63]=[CH:64][C:59]([N+:56]([O-:58])=[O:57])=[C:60]([C:72]([F:73])([F:74])[F:75])[CH:61]=2)[CH2:67][CH2:68]1)=[O:5]

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 43448257N-(4-Nitro-3-(trifluoromethyl)phenyl)piperidin-4-amineHCID 867194912-Methyl-3-[4-[6-(trifluoromethyl) quinolin-2-yl]piperazin-1-yl]propanoic acid

Produkt 1

HCID 867194902-Methyl-1-(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]piperidin-1-yl)-3-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]propan-1-oneAusbeute 64,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 2-methyl-3-[4-[6-(trifluoromethyl) quinolin-2-yl]piperazin-1-yl]propanoic acid (100 mg, 0.27 mmol) in dichloromethane (20 ml) was added EDAC.HCl (79 mg, 0.41 mmol, 1.5 eq.), 1H-1,2,3-benzotriazol-1-ol (55.2 mg, 0.41 mmol, 1.5 eq.), triethylamine (82.6 mg, 0.82 mmol, 3 eq.) and N-[4-nitro-3-(trifluoromethyl)phenyl]piperidin-4-amine (94.5 mg, 0.33 mmol, 1.2 eq.). The resulting solution was stirred overnight at room temperature and then quenched by the addition of water (50 ml) and extracted with dichloromethane (3×30 ml). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under vacuum to give a residue, which was purified by Prep-TLC with 5% methanol in dichloromethane to afford of 2-methyl-1-(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]piperidin-1-yl)-3-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]propan-1-one as a yellow solid (111.2 mg, 64%). (ES, m/z): [M+H]+ 639.40; 1H NMR (300 MHz, CDCl3): δ 7.95-8.08 (m, 1H), 7.72 (overlapping m, 2H), 7.01 (d, J=9.3 Hz, 1H), 6.89 (m, 1H), 6.65 (m, 1H), 4.49-4.70 (m, 2H), 4.08 (m, 1H), 3.72-3.85 (br m, 5H), 3.65 (m, 1H), 3.08 (br s, 1H), 2.88 (br m, 2H), 2.68 (br s, 3H), 2.38 (m, 1H), 2.07-2.20 (overlapping m, 2H), 1.47 (m, 2H), 1.13 (br s, 3H).

Aufarbeitung

  1. customquenched by the addition of water (50 ml)
  2. extractionextracted with dichloromethane (3×30 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customto give a residue, which
  6. customwas purified by Prep-TLC with 5% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-a3e0739d300b442c9ad8f4c7244753de
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09249102B2

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