Triethylamine → 1-[4-(2,3-Dihydro-1-benzofuran-2-ylmethyl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one

HRID 1772219Notes

Reaction equation

HRID 1772219 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]([OH:21])=O)[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.[O:55]1[C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][C:58]=2[CH2:57][CH:56]1[CH2:64][N:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1>ClCCl>[O:55]1[C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][C:58]=2[CH2:57][CH:56]1[CH2:64][N:65]1[CH2:70][CH2:69][N:68]([C:19](=[O:21])[CH2:18][O:17][CH:14]2[CH2:15][CH2:16][CH:11]([NH:10][C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:22]([F:25])([F:24])[F:23])[CH:6]=3)[CH2:12][CH2:13]2)[CH2:67][CH2:66]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 31596641-(2,3-Dihydro-benzofuran-2-ylmethyl)-piperazineHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 867194741-[4-(2,3-Dihydro-1-benzofuran-2-ylmethyl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-oneYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 2-[(4-[4-nitro-3-(trifluoromethyl)phenyl]aminocyclohexyl)oxy]acetic acid (900 mg, 2.48 mmol) in dichloromethane (50 ml) was added EDAC.HCl (661 mg, 3.45 mmol), HOBt (464 mg, 3.43 mmol), triethylamine (463 mg, 4.58 mmol) and 1-(2,3-dihydro-1-benzofuran-2-ylmethyl)piperazine (500 mg, 2.29 mmol) in dichloromethane (1 ml) with stirring for overnight at room temperature. Then the mixture was diluted with dichloromethane (300 ml) and washed with water (100 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to give a residue, which was purified by a silica gel column, eluted with 0.5%-3% methanol in dichloromethane to afford 1-[4-(2,3-dihydro-1-benzofuran-2-ylmethyl)piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (462.4 mg, 36%); (ES, m/z): [M+H]+ 563.00; 1H NMR (300 MHz, CDCl3): δ 8.00 (d, J=8.7 Hz, 1H), 7.09-7.18 (m, 2H), 6.77-6.88 (m, 3H), 6.61 (dd, J=2.1 Hz, 8.7 Hz, 1H), 5.03 (broad s, 1H), 4.45 (d, J=6.9 Hz, 1H), 4.20 (s, 2H), 3.67-3.78 (m, 3H), 3.40-3.49 (m, 3H), 2.66-2.99 (m. 6H), 2.13-2.23 (m, 4H), 1.41-1.63 (m, 3H), 1.21-1.34 (m, 3H).

Workup

  1. washwashed with water (100 ml)
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto give a residue, which
  6. customwas purified by a silica gel column
  7. washeluted with 0.5%-3% methanol in dichloromethane

Sources & evidence

ORD record
ord-6b32a47ccf0d434fa2051de5cf98d1d4
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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