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

HRID 1772213Notes

Reaction equation

HRID 1772213 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].[N:26]1([C:32]2[CH:41]=[CH:40][C:39]3[C:34](=[CH:35][CH:36]=[C:37]([C:42]([F:45])([F:44])[F:43])[CH:38]=3)[N:33]=2)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>ClCCl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:12][CH2:13][CH:14]([O:17][CH2:18][C:19]([N:29]3[CH2:30][CH2:31][N:26]([C:32]4[CH:41]=[CH:40][C:39]5[C:34](=[CH:35][CH:36]=[C:37]([C:42]([F:45])([F:43])[F:44])[CH:38]=5)[N:33]=4)[CH2:27][CH2:28]3)=[O:20])[CH2:15][CH2:16]2)=[CH:6][C:5]=1[C:22]([F:23])([F:24])[F:25])([O-:3])=[O:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acidHCID 867194712-(Piperazin-1-yl)-6-(trifluoromethyl)quinoline

Product 1

HCID 867194722-[(4-[[4-Nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]-1-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]ethan-1-oneYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[(4-[4-nitro-3-(trifluoromethyl)phenyl]aminocyclohexyl)oxy]acetic acid (100 mg, 0.28 mmol) in dichloromethane (20 ml) was added 2-(piperazin-1-yl)-6-(trifluoromethyl)quinoline (93.1 mg, 0.33 mmol, 1.2 eq), EDAC.HCl (79 mg, 0.41 mmol, 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), Et3N (84 mg, 0.83 mmol, 3 eq). The resulting solution was stirred overnight at room temperature and then quenched by the addition of water (50 ml), extracted with of dichloromethane (3×30 ml) and the organic layers were combined and dried over anhydrous sodium sulfate. The organic solution was filtered and then concentrated under vacuum. The crude material was purified by Pre-TLC using 4% methanol in dichloromethane to elute. Concentration of the product-containing fractions afforded 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]-1-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]ethan-1-one as a yellow solid (77 mg, 45%). (ES, m/z): [M+H]+ 626.40. 1H NMR (300 MHz, CD3OD): δ 8.13 (d, J=9.0 Hz, 1H), 8.02-8.05 (t, J=4.5 Hz, 2H), 7.42-7.79 (m, 2H), 7.29 (d, J=9.3 Hz, 1H), 6.99 (d, J=2.4 Hz, 1H), 6.78-6.81 (dd, J=2.4, 9.2 Hz, 1H), 4.34 (s, 2H), 3.88-3.94 (m, 4H), 3.72-3.78 (m, 4H), 3.45-3.50 (m, 2H), 2.10-2.20 (m, 4H), 1.34-1.54 (m, 4H).

Workup

  1. customquenched by the addition of water (50 ml)
  2. extractionextracted with of dichloromethane (3×30 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe organic solution was filtered
  5. concentrationconcentrated under vacuum
  6. customThe crude material was purified by Pre-TLC
  7. washto elute

Sources & evidence

ORD record
ord-73d0b2657ca846a0bd4a30578a319766
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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