Triethylamine → 1-[4-(4-Methylquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoro-methyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one

HRID 1772215Notes

Reaction equation

HRID 1772215 reaction equation
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[N+:47]([C:50]1[CH:55]=[CH:54][C:53]([NH:56][CH:57]2[CH2:62][CH2:61][CH:60]([O:63][CH2:64][C:65](O)=[O:66])[CH2:59][CH2:58]2)=[CH:52][C:51]=1[C:68]([F:71])([F:70])[F:69])([O-:49])=[O:48]>ClCCl>[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([N:12]2[CH2:17][CH2:16][N:15]([C:65](=[O:66])[CH2:64][O:63][CH:60]3[CH2:61][CH2:62][CH:57]([NH:56][C:53]4[CH:54]=[CH:55][C:50]([N+:47]([O-:49])=[O:48])=[C:51]([C:68]([F:70])([F:69])[F:71])[CH:52]=4)[CH2:58][CH2:59]3)[CH2:14][CH2:13]2)[CH:3]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 5987544-Methyl-2-piperazin-1-yl-quinolineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 867194731-[4-(4-Methylquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoro-methyl)phenyl]amino]cyclohexyl)oxy]ethan-1-oneYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-methyl-2-(piperazin-1-yl)quinoline (100 mg, 0.44 mmol) in dichloromethane (20 ml) was added EDAC.HCl (126 mg, 0.66 mmol, 1.5 eq), HOBt (88.8 mg, 0.66 mmol, 1.5 eq), triethylamine (133 mg, 1.31 mmol, 3 eq) and 2-[(4-[4-nitro-3-(trifluoromethyl)phenyl]aminocyclohexyl)oxy]acetic acid (190 mg, 0.52 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, filtered, and then concentrated under vacuum to give a residue. The crude material was purified by Pre-TLC with 50% ethyl acetate in dichloromethane to afford 1-[4-(4-methylquinolin-2-yl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoro-methyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (117 mg, 47%); (ES, m/z) [M+H]+ 572.20; 1H NMR (300 MHz, CDCl3): δ 8.02 (d, J=9.0 Hz, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.74 (s, 1H), 7.54-7.62 (m, 1H), 7.32-7.38 (m, 1H), 6.87 (s, 2H), 6.63-6.67 (m, 1H), 4.48 (d, J=7.5 Hz, 1H), 4.28 (s, 2H), 3.75-3.85 (m, 7H), 3.39-3.52 (m, 2H), 2.65 (s, 3H), 2.16 (d, J=9.9 Hz, 1H), 1.46-1.53 (m, 2H), 1.25-1.36 (m, 2H).

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. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto give a residue
  7. customThe crude material was purified by Pre-TLC with 50% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-49411e8632d44f2a9f215a2ca531e471
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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