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

HRID 62726

反応式

HRID 62726 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

HCID 67041919Methyl 6-(3,5-dichloro-4-ethoxyphenylcarbamoyl)nicotinate収率 45.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f2510055109f4a3c94bc657e1c279bab
出典データセット
uspto-grants-2016_09
特許番号
US09447028B2

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