Triethylamine → 1-[4-[(5-Chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one

HRID 1772247Notes

Reaction equation

HRID 1772247 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.[Cl:55][C:56]1[CH:57]=[CH:58][C:59]2[O:63][CH:62]([C:64]([N:66]3[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]3)=[O:65])[CH2:61][C:60]=2[CH:72]=1>ClCCl>[Cl:55][C:56]1[CH:57]=[CH:58][C:59]2[O:63][CH:62]([C:64]([N:66]3[CH2:67][CH2:68][N:69]([C:19](=[O:21])[CH2:18][O:17][CH:14]4[CH2:13][CH2:12][CH:11]([NH:10][C:7]5[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:22]([F:24])([F:25])[F:23])[CH:6]=5)[CH2:16][CH2:15]4)[CH2:70][CH2:71]3)=[O:65])[CH2:61][C:60]=2[CH:72]=1

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 867194831-[(5-Chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine

Product 1

HCID 867194841-[4-[(5-Chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-oneYield 20.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (80 mg, 0.42 mmol 1.5 eq), HOBt (56 mg, 0.41 mmol, 1.5 eq), triethylamine (84 mg, 0.83 mmol, 3 eq) and 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazine (74 mg, 0.28 mmol, 1 eq). The resulting solution was stirred overnight at room temperature and then concentrated under vacuum. The crude residue was purified by silica gel chromatography using 5-20% ethyl acetate in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 1-[4-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)carbonyl]piperazin-1-yl]-2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethan-1-one as a yellow solid (34.9 mg, 19%). (ES, m/z): [M+H]+ 611.25; 1H NMR (300 MHz, CDCl3): δ 8.00 (d, J=9.0 Hz, 1H), 7.18 (s, 1H), 7.07 (d, J=8.4 Hz, 1H), 6.85 (d, J=2.1 Hz, 1H), 6.70 (d, J=8.7 Hz, 1H), 6.63 (dd, J=2.1 Hz, 9.0 Hz, 1H), 5.42 (dd, J=7.5 Hz, 9.0 Hz, 1H), 4.23 (s, 2H), 3.82-3.98 (m, 4H), 3.30-3.70 (m, 8H), 2.10-2.20 (m, 4H), 1.42-1.58 (m, 2H), 1.20-1.40 (m, 2H).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude residue was purified by silica gel chromatography
  3. washto elute
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2bdd3bdeef5c46b4af13f51dabf6beed
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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