1,2-Dichloroethane → N-(6-(cyanomethyl)-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride

HRID 576217Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 576217
[NH2:1][C:2]1[CH:3]=[C:4]([C:11]([F:14])([F:13])[F:12])[C:5]([CH2:8][C:9]#[N:10])=[N:6][CH:7]=1.[CH2:15]([O:17][C:18]1[C:23](=[O:24])[NH:22][CH:21]=[C:20]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31][C:32](O)=[O:33])=[C:27]([F:35])[CH:26]=2)[CH:19]=1)[CH3:16].C1C=CC2N(O)N=NC=2C=1.C(Cl)C[Cl:48].CCN(CC)CC>CN(C=O)C>[ClH:48].[C:9]([CH2:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][C:32](=[O:33])[CH2:31][C:28]2[CH:29]=[CH:30][C:25]([C:20]3[CH:19]=[C:18]([O:17][CH2:15][CH3:16])[C:23](=[O:24])[NH:22][CH:21]=3)=[CH:26][C:27]=2[F:35])=[CH:3][C:4]=1[C:11]([F:14])([F:12])[F:13])#[N:10]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 904154342-(4-(5-Ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetic acidHCID 904165325-Amino-3-(trifluoromethyl)pyridine-2-acetonitrile

Produkt 1

HCID 90422662N-(6-(cyanomethyl)-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochlorideAusbeute 2,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A suspension of 2-(5-amino-3-(trifluoromethyl)pyridin-2-yl)acetonitrile (16.00 mg, 0.080 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 (46.33 mg, 0.080 mmol) in DMF (5 mL). HOBt (18.27 mg, 0.119 mmol), EDC (22.87 mg, 0.119 mmol) and Et3N (0.033 mL, 0.239 mmol) and the mixture was 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 a yellow solid of N-(6-(cyanomethyl)-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride (0.96 mg, 1.879 μmol, 2.4% yield). TLC (DCM/MeOH=10:1, Rf=0.3): 1H NMR (400 MHz, CD3OD) δ: 8.87-8.96 (m, 1H), 8.56 (d, J=2.21 Hz, 1H), 7.19-7.50 (m, 5H), 4.08-4.18 (m, 2H), 3.85 (s, 3H), 3.58 (s, 2H), 1.29-1.35 (m, 3H); ES-LCMS m/z 475.0 (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-7656bc887c7a44058aa8fa7eee8b5e59
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09035063B2

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