1,1'-Carbonyldiimidazole → Methyl 6-(3,5-dichloro-4-ethoxyphenylcarbamoyl)nicotinate

HRID 62726

Reaktionsgleichung

Reaktionsgleichung von HRID 62726
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=1)=[O:4].C1N=CN(C(N2C=NC=C2)=O)C=1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:31]=[C:32]([Cl:37])[C:33]=1[O:34][CH2:35][CH3:36])[NH2:30].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:26][C:27]1[CH:28]=[C:29]([NH:30][C:11]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][N:9]=2)=[O:13])[CH:31]=[C:32]([Cl:37])[C:33]=1[O:34][CH2:35][CH3:36]

Komponenten

6

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 3149925-(Methoxycarbonyl)pyridine-2-carboxylic acidHCID 152708843,5-Dichloro-4-ethoxyaniline

Produkt 1

HCID 67041919Methyl 6-(3,5-dichloro-4-ethoxyphenylcarbamoyl)nicotinateAusbeute 45,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

5-(Methoxycarbonyl)-2-pyridine carboxylic acid (50 mg, 276 μmol) was dissolved in DMF (2 mL) and treated with CDI (60 mg, 370 μmol). The reaction mixture was stirred at RT for 2 h. 3,5-Dichloro-4-ethoxyaniline (2) (57 mg, 276 μmol) and DIPEA (96 μL, 552 μmol) were added sequentially and the reaction mixture was stirred at RT overnight, then at 70° C. for 19 h. The reaction mixture was partitioned between EtOAc and aqueous HCl (1 M). The organic layer was washed successively with water and brine, and then dried over MgSO4, filtered and concentrated in vacuo. The residue was crystallised from methanol to afford methyl 6-(3,5-dichloro-4-ethoxyphenylcarbamoyl)nicotinate (3) (46 mg, 45%) as a white solid: m/z 369 [M+H]+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 11.12 (1H, s), 9.18 (1H, dd), 8.55 (1H, dd), 8.29 (1H, dd), 8.13 (2H, s), 4.06 (2H, q), 3.94 (3H, s), 1.37 (3H, t).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at RT overnight
  2. waitat 70° C. for 19 h
  3. customThe reaction mixture was partitioned between EtOAc and aqueous HCl (1 M)
  4. washThe organic layer was washed successively with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was crystallised from methanol

Quellen und Nachweise

ORD-Eintrag
ord-f2510055109f4a3c94bc657e1c279bab
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447028B2

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