Triethylamine → 1-[4-(6-Fluoroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one

HRID 1772204Notes

Reaction equation

HRID 1772204 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:22]([F:25])([F:24])[F:23])([O-:3])=[O:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[F:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][CH:65]=1)[N:62]=[C:61]([N:66]1[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]1)[CH:60]=[CH:59]2>ClCCl>[F:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][CH:65]=1)[N:62]=[C:61]([N:66]1[CH2:67][CH2:68][N:69]([C:19](=[O:20])[CH2:18][O:17][CH:14]3[CH2:15][CH2:16][CH:11]([NH:10][C:7]4[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:22]([F:23])([F:24])[F:25])[CH:6]=4)[CH2:12][CH2:13]3)[CH2:70][CH2:71]1)[CH:60]=[CH:59]2

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 442203176-Fluoro-2-piperazin-1-yl-quinolineHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 747667751-[4-(6-Fluoroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-oneYield 49.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl) oxy]acetic acid (100 mg, 0.28 mmol) in dichloromethane (20 ml) was added EDAC.HCl (79.1 mg, 0.41 mmol), HOBt (55.9 mg, 0.41 mmol), triethylamine (83.7 mg, 0.83 mmol) and 6-fluoro-2-(piperazin-1-yl)quinoline (70.2 mg, 0.30 mmol) at room temperature. After stirred overnight, the reaction mixture was then diluted with dichloromethane (100 ml) and washed with water (2×100 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to give a residue, which was purified by a silica gel column with 2% methanol in dichloromethane to afford 1-[4-(6-fluoroquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (80 mg, 48%); (ES, m/z): [M+H]+ 576.20; 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J=8.8 Hz, 1H), 7.94-7.99 (m, 1H), 7.72-7.78 (m, 1H), 7.31-7.37 (m, 2H), 7.02 (t, J=8.0 Hz, 1H), 6.87 (s, 1H), 6.64 (dd, J=2.4 Hz, 9.2 Hz, 1H), 4.48 (d, J=7.6 Hz, 1H), 4.28 (s, 2H), 3.75-3.81 (m, 7H), 3.41-3.49 (m, 2H), 2.17-2.19 (m, 4H), 1.50-1.58 (m, 2H), 1.28-1.36 (m, 3H).

Workup

  1. washwashed with water (2×100 ml)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto give a residue, which
  6. customwas purified by a silica gel column with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-cf780b5642b64e1f850525eded53f65b
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

Loading…