Triethylamine → HCID 86719481, compound

HRID 1772232Notes

Reaction equation

HRID 1772232 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.[F:55][C:56]([F:74])([F:73])[C:57]1[CH:58]=[CH:59][C:60]2[O:64][CH:63]([CH2:65][N:66]3[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]3)[CH2:62][C:61]=2[CH:72]=1>ClCCl.O>[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:69]3[CH2:70][CH2:71][N:66]([CH2:65][CH:63]4[CH2:62][C:61]5[CH:72]=[C:57]([C:56]([F:74])([F:55])[F:73])[CH:58]=[CH:59][C:60]=5[O:64]4)[CH2:67][CH2:68]3)=[O:21])[CH2:15][CH2:16]2)=[CH:6][C:5]=1[C:22]([F:25])([F:23])[F:24])([O-:3])=[O:2]

Participants

8

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 86719479HCID 86719479, compound

Product 1

HCID 86719481HCID 86719481, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (30 ml) was added EDAC.HCl (79.6 mg, 0.42 mmol, 1.5 eq), HOBt (55.9 mg, 0.41 mmol, 1.5 eq), triethylamine (55.9 mg, 0.55 mmol, 1.5 eq) and 1-[[5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl]piperazine (86.9 mg, 0.30 mmol, 1.1 eq). The solution was stirred at room temperature overnight. The reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×30 ml). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 25% ethyl acetate in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]-1-(4-[[5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl]piperazin-1-yl)ethan-1-one as a yellow solid (69.9 mg, 40%); (ES, m/z): [M+H]+ 631.20; 1H NMR (300 MHz, CDCl3): δ 8.01 (d, J=9.0 Hz, 1H), 7.44 (m, 2H), 6.84 (m, 2H), 6.62 (dd, J=2.7 Hz, 9.0 Hz, 1H), 5.10 (broad s, 1H), 4.47 (d, J=8.1 Hz, 1H), 4.22 (s, 2H), 3.61-3.82 (m, 3H), 3.36-3.48 (m, 3H), 3.01-3.07 (dd, J=7.8 Hz, 16.2 Hz, 1H), 2.80-2.95 (m, 1H), 2.54-2.74 (m, 4H), 2.12-2.18 (m, 4H), 1.43-1.59 (m, 3H), 1.24-1.35 (m, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×30 ml)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified by silica gel chromatography
  6. washto elute
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-f0d5f7a97a314d41a2a0d5d93a77f6c1
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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