Ethanolamine → N-(2-hydroxyethyl)-1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxamide

HRID 2111803ノート

反応式

HRID 2111803 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.C1C=CC2N(O)N=NC=2C=1.C(N=C=NC(C)C)(C)C.[NH2:48][CH2:49][CH2:50][OH:51].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(Cl)Cl>[OH:51][CH2:50][CH2:49][NH:48][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

9

反応物 5

HCID 700EthanolamineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 576397141-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxylic acid

生成物 1

HCID 67012607N-(2-hydroxyethyl)-1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxamide

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a 20 mL Bohdan MiniBlock 12-position glass reaction tube, 1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxylic acid (100 mg, 0.27 mmol), PS-HOBt (HL; 269 mg, 0.24 mmol), DMAP (18 mg, 0.15 mmol), CH2Cl2 (1 mL), and DMF (0.25 mL) were added. The reaction mixture was shaken for 5 min. 1,3-Diisopropylcarbodiimide (138 mg, 1.09 mmol) was added to the reaction mixture and shaken for 4 h. The solution was filtered and the resin was washed with CH2Cl2 (3×3 mL), DMF (3×3 mL), and THF (3×3 mL). The resin was resuspended in DMF (1 mL) and 2-aminoethanol (15 mg, 0.24 mmol) and DIEA (31 mg, 0.24 mmol) were added. The reaction mixture was allowed to shake overnight. The reaction mixture was then filtered, and washed with CH2Cl2 (3×3 mL), DMF (3×3 mL), and THF (3×3 mL). The filtrate and the washes were combined and concentrated in vacuo. The crude product was purified by using the Waters mass-directed HPLC purification system to yield N-(2-hydroxyethyl)-1-{4-[2-(pyridin-2-yloxy)ethoxy]phenyl}-1H-benzimidazole-5-carboxamide as a yellowish white powder. 1H NMR (d6-DMSO, 400 MHz): δ 8.57 (s, 1H), 8.49 (t, J=4.4 Hz, 1H), 8.32 (d, J=1.2 Hz, 1H), 8.19 (ddd, J=5.2, 2.0, 0.8 Hz, 1H), 7.85 (dd, J=8.4, 1.6 Hz, 1H), 7.74 (ddd, J=9.2, 7.2, 2.0 Hz, 1H), 7.61 (ddd, J=5.6, 3.6, 3.6 Hz, 2H), 7.56 (d, J=8.0 Hz, 1H), 7.23 (ddd, J=6.0, 3.6, 3.6 Hz, 2H), 7.01 (ddd, J=7.2, 5.2, 0.8 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 419 (60) [MH+].

後処理

  1. additionwere added
  2. stirringshaken for 4 h
  3. filtrationThe solution was filtered
  4. washthe resin was washed with CH2Cl2 (3×3 mL), DMF (3×3 mL), and THF (3×3 mL)
  5. waitto shake overnight
  6. filtrationThe reaction mixture was then filtered
  7. washwashed with CH2Cl2 (3×3 mL), DMF (3×3 mL), and THF (3×3 mL)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified
  10. customthe Waters mass-directed HPLC purification system

出典と根拠

ORDレコード
ord-1ec28bd7fd024e539b14e12b99d070fb
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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