Triethylamine → HCID 86719485, compound

HRID 1772251Notes

Reaction equation

HRID 1772251 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][CH:13]([O:16][CH2:17][C:18]([OH:20])=O)[CH2:12][CH2:11]2)=[CH:5][C:4]=1[C:21]([F:24])([F:23])[F:22])#[N:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[F:54][C:55]([F:73])([F:72])[C:56]1[CH:57]=[CH:58][C:59]2[O:63][CH:62]([CH2:64][N:65]3[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]3)[CH2:61][C:60]=2[CH:71]=1>ClCCl>[O:20]=[C:18]([N:68]1[CH2:69][CH2:70][N:65]([CH2:64][CH:62]2[CH2:61][C:60]3[CH:71]=[C:56]([C:55]([F:73])([F:54])[F:72])[CH:57]=[CH:58][C:59]=3[O:63]2)[CH2:66][CH2:67]1)[CH2:17][O:16][CH:13]1[CH2:12][CH2:11][CH:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:21]([F:23])([F:22])[F:24])[CH:5]=2)[CH2:15][CH2:14]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67283106HCID 67283106, compoundHCID 86719479HCID 86719479, compound

Product 1

HCID 86719485HCID 86719485, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[(4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetic acid (100 mg, 0.29 mmol) in dichloromethane (30 ml) was added EDAC.HCl (84.2 mg, 0.44 mmol, 1.5 eq), HOBt (59.2 mg, 0.44 mmol, 1.5 eq), triethylamine (59.1 mg, 0.58 mmol, 2 eq) and 1-[[5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl]piperazine (92.0 mg, 0.32 mmol, 1.1 eq). The reaction mixture was stirred overnight at room temperature and then quenched by the addition of water (30 ml). The crude product was extracted with ethyl acetate (3×20 ml). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated under vacuum. The crude material was purified by Pre-TLC with 20% ethyl acetate in dichloromethane to afford 4-([4-[2-oxo-2-(4-[[5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl]piperazin-1-yl)ethoxy]cyclohexyl]amino)-2-(trifluoromethyl)benzonitrile as a white solid (76 mg, 43%); (ES, m/z): [M+H]+ 611.30; 1H NMR (300 MHz, CDCl3): δ 7.55 (d, J=8.7 Hz, 1H), 7.42 (m, 2H), 6.81-6.86 (m, 2H), 6.64-6.68 (dd, J=2.1 Hz, 8.4 Hz, 1H), 5.08-5.13 (m, 1H), 4.29 (d, J=7.8 Hz, 1H), 4.21 (s, 2H), 3.65-3.78 (m, 3H), 3.30-3.48 (m, 3H), 3.01-3.06 (dd, J=8.4 Hz, 15.9 Hz, 2H), 2.51-2.90 (m, 4H), 2.10-2.19 (m, 4H), 1.44-1.58 (m, 3H), 1.21-1.33 (m, 3H).

Workup

  1. customquenched by the addition of water (30 ml)
  2. extractionThe crude product was extracted with ethyl acetate (3×20 ml)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude material was purified by Pre-TLC with 20% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-297853ccab4048a9ac4a4df095b2ee81
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

Loading…