Triethylamine → HCID 86719515, compound

HRID 1772278Notes

Reaction equation

HRID 1772278 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[CH:5][C:6]2[O:10][CH:9]([CH2:11][NH:12][C:13]([C:15]([O:17][Li])=O)=[O:14])[CH2:8][C:7]=2[CH:19]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[NH2:51][CH2:52][CH2:53][O:54][CH:55]1[CH2:60][CH2:59][CH:58]([NH:61][C:62]2[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[C:64]([C:71]([F:74])([F:73])[F:72])[CH:63]=2)[CH2:57][CH2:56]1>CN(C)C=O.O>[N+:68]([C:65]1[CH:66]=[CH:67][C:62]([NH:61][CH:58]2[CH2:57][CH2:56][CH:55]([O:54][CH2:53][CH2:52][NH:51][C:15](=[O:17])[C:13]([NH:12][CH2:11][CH:9]3[CH2:8][C:7]4[CH:19]=[C:3]([C:2]([F:1])([F:21])[F:20])[CH:4]=[CH:5][C:6]=4[O:10]3)=[O:14])[CH2:60][CH2:59]2)=[CH:63][C:64]=1[C:71]([F:72])([F:73])[F:74])([O-:70])=[O:69]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86719488HCID 86719488, compoundHCID 178506951HCID 178506951, compound

Product 1

HCID 86719515HCID 86719515, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

The mixture of lithio ([[5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl]carbamoyl)formate (170 mg, 0.58 mmol), EDAC.HCl (166 mg, 0.87 mmol), HOBt (58.3 mg, 0.43 mmol) and triethylamine (87.3 mg, 0.86 mmol) in N,N-dimethylformamide (10 ml) was stirred for 1 hour before the addition of N-[4-(2-aminoethoxy)cyclohexyl]-4-nitro-3-(trifluoromethyl)aniline (100 mg, 0.29 mmol). The resulting solution was stirred overnight at room temperature, diluted with water (100 ml), and extracted with dichloromethane (3×50 ml). The organic fractions were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by HPLC to afford N1-[2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethyl]-N2-[[5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl]ethanediamide as a yellow solid (52 mg, 29%). (ES, m/z): [M+H]+ 619.10; 1H NMR (300 MHz, CDCl3): δ 8.02 (d, J=9.3 Hz, 1H), 7.80 (br s, 1H), 7.72 (br s, 1H), 7.41 (m, 2H), 6.84 (m, 2H), 6.63 (dd, J=9.0, 2.4 Hz, 1H), 5.00 (m, 1H), 3.78 (m, 1H), 3.60-3.55 (m, 3H), 3.53-3.50 (m, 2H), 3.35 (br m, 3H), 2.98 (dd, J=16.2, 7.2 Hz, 1H), 2.12 (m, 4H), 1.46-1.34 (m, 2H), 1.29-1.22 (m, 2H).

Workup

  1. extractionextracted with dichloromethane (3×50 ml)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-06f34c97a7ba4de3bb4e3befc7fee733
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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