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

HRID 2111803Notes

Reaction equation

HRID 2111803 reaction equation
[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]

Participants

9

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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+].

Workup

  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

Sources & evidence

ORD record
ord-1ec28bd7fd024e539b14e12b99d070fb
Source dataset
uspto-grants-2009_04
Patent number
US07521448B2

Reaction notes

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