1,1'-Carbonyldiimidazole → N-methyl-1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxamide

HRID 2111802ノート

反応式

HRID 2111802 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C:21]3[CH:22]=[CH:23][C:24]([C:26](O)=[O:27])=[CH:25][C:20]=3[N:19]=[CH:18]2)=[CH:13][CH:12]=1.[C:29](N1C=CN=C1)([N:31]1C=CN=C1)=O.Cl.CN.CCN(C(C)C)C(C)C>C1COCC1>[CH3:29][NH:31][C:26]([C:24]1[CH:23]=[CH:22][C:21]2[N:17]([C:14]3[CH:13]=[CH:12][C:11]([O:10][CH2:9][CH2:8][O:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[CH:16][CH:15]=3)[CH:18]=[N:19][C:20]=2[CH:25]=1)=[O:27]

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 576397141-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxylic acid

生成物 1

HCID 67011308N-methyl-1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

1-{4-[2-(Pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxylic acid (100 mg, 0.266 mmol) and 1,1′-carbonyldiimidazole (86 mg, 0.53 mmol) were dissolved in dry THF (2 mL) under a N2 atmosphere. The reaction mixture was heated at 60° C. for 1 h and then cooled to rt. Methylamine hydrochloride (27 mg, 0.40 mmol) and N,N′-diisopropylethylamine (52 mg, 0.40 mmol, 70 μL) were added and the reaction was allowed to stir at rt. After 18 h, the reaction mixture was concentrated in vacuo, diluted with CH2Cl2 (2 mL), and washed with distilled water (1 mL). The aqueous phase was back extracted with CH2Cl2 (2 mL×5) and the combined organic extracts were concentrated in vacuo. The resulting yellow solid was purified using the Waters mass-directed HPLC purification system to give N-methyl-1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxamide as a white powder. 1H NMR (d6-DMSO, 400 MHz): δ 8.57 (s, 1H), 8.49 (brq, J=4.4 Hz, 1H), 8.28 (d, J=1.2 Hz, 1H), 8.19 (ddd, J=5.2, 2.0, 0.8 Hz, 1H), 7.85 (dd, J=8.6, 1.4 Hz, 1H), 7.74 (ddd, J=8.8, 6.8, 2.0 Hz, 1H), 7.61 (ddd, J=5.2, 3.2, 3.2 Hz, 2H), 7.55 (d, J=9.2 Hz, 1H), 7.23 (ddd, J=5.8, 3.6, 3.6 Hz, 2H), 7.01 (ddd, J=7.2, 5.2, 1.2 Hz, 1H), 6.88 (ddd, J=8.4, 0.8, 0.8 Hz, 1H), 4.63 (m, 2H), 4.43 (m, 2H), 2.82 (d, J=4.8 Hz, 3H). MS(ES+): m/z 389 [MH+].

後処理

  1. temperaturecooled to rt
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. additiondiluted with CH2Cl2 (2 mL)
  4. washwashed with distilled water (1 mL)
  5. extractionThe aqueous phase was back extracted with CH2Cl2 (2 mL×5)
  6. concentrationthe combined organic extracts were concentrated in vacuo
  7. customThe resulting yellow solid was purified
  8. customthe Waters mass-directed HPLC purification system

出典と根拠

ORDレコード
ord-5db542b4a1fc41bfbeaa46f55044a2af
出典データセット
uspto-grants-2009_04
特許番号
US07521448B2

反応ノート

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