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 1772256Notes

Reaction equation

HRID 1772256 reaction equation
[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]

Participants

7

Reactant 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

Product 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-oneYield 64.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a3e0739d300b442c9ad8f4c7244753de
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

Loading…