1,2-Dichloroethane → 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)acetamide, hydrochloride

HRID 576210Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 576210
[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:8]=[C:9]([CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)[NH2:10])[CH:6]=1.[CH2:18]([O:20][C:21]1[C:26](=[O:27])[NH:25][CH:24]=[C:23]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C:35](O)=[O:36])=[C:30]([F:38])[CH:29]=2)[CH:22]=1)[CH3:19].C1C=CC2N(O)N=NC=2C=1.C(Cl)C[Cl:51].CCN(CC)CC>CN(C=O)C>[ClH:51].[CH2:18]([O:20][C:21]1[C:26](=[O:27])[NH:25][CH:24]=[C:23]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C:35]([NH:10][C:9]3[CH:11]=[C:12]([C:14]([F:17])([F:15])[F:16])[CH:13]=[C:7]([N:5]4[CH:6]=[C:2]([CH3:1])[N:3]=[CH:4]4)[CH:8]=3)=[O:36])=[C:30]([F:38])[CH:29]=2)[CH:22]=1)[CH3:19]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 120028253-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)anilineHCID 904154342-(4-(5-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid

Produkt 1

HCID 904230892-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)acetamide, hydrochlorideAusbeute 10,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A suspension of 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline (6.63 mg, 0.027 mmol) in DMF (5 mL) was added to a solution of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acid (8 mg, 0.027 mmol) in DMF (5 mL). HOBt (6.31 mg, 0.041 mmol), EDC (7.90 mg, 0.041 mmol) and Et3N (0.011 mL, 0.082 mmol) were added and the mixture was stirred at 50° C. for 12 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition) to yield an off white solid of 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)acetamide, hydrochloride (1.60 mg, 2.90 μmol, 10.6% yield). TLC (DCM/MeOH=10:1, Rf=0.3): 1H NMR (400 MHz, CD3OD) δ: 9.41 (d, J=1.54 Hz, 1H), 8.37-8.45 (m, 1H), 7.96 (s, 1H), 7.73-7.88 (m, 2H), 7.18-7.52 (m, 5H), 4.14 (q, J=7.06 Hz, 2H), 3.87 (s, 2H), 2.43 (s, 3H), 1.46 (t, J=6.95 Hz, 3H); ES-LCMS m/z 515.1 (M+H).

Aufarbeitung

  1. concentrationThen the solution was concentrated
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, acidic condition)

Quellen und Nachweise

ORD-Eintrag
ord-9b15854275034769aacfac4facb1259a
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09035063B2

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