Sodium hydride → HCID 11419939, compound

HRID 2111796Notes

Reaction equation

[OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([C:20]([NH:22][CH2:23][C:24]4[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=4)=[O:21])=[CH:19][C:14]=3[N:13]=[CH:12]2)=[CH:7][CH:6]=1.[H-].[Na+].[H][H].Cl[C:35]1[CH:40]=[N:39][CH:38]=[CH:37][N:36]=1>CN(C=O)C>[N:36]1[CH:37]=[CH:38][N:39]=[CH:40][C:35]=1[O:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([C:20]([NH:22][CH2:23][C:24]4[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=4)=[O:21])=[CH:19][C:14]=3[N:13]=[CH:12]2)=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

1-[4-(2-Hydroxyethoxy)phenyl]-N-(pyridin-3-ylmethyl)-1H-benzimidazole-5-carboxamide (100 mg, 0.26 mmol) and sodium hydride (6 mg, 0.26 mmol) were dissolved in anhydrous DMF (2 mL) under N2 atmosphere. The reaction mixture was heated to 60° C. until hydrogen gas evolution ceased. 2-Chloropyrazine (35 mg, 0.31 mmol, 28 μL) was then added drop-wise and the reaction was heated to 100° C. After 18 h, the reaction mixture was concentrated in vacuo and purified by mass-directed purification to provide 1-{4-[2-(Pyrazin-2-yloxy)ethoxy]phenyl}-N-(pyridin-3-ylmethyl)-1H-benzimidazole-5-carboxamide (OSIP484814AA) as a white powder. 1H NMR (d6-DMSO, 400 MHz): δ 9.17 (brt, J=6.0 Hz, 1H), 8.60 (s, 1H), 8.58 (d, J=1.6 Hz, 1H), 8.47 (dd, J=5.2, 1.2 Hz, 1H), 8.40 (d, J=0.8 Hz, 1H), 8.37 (d, J=1.2 Hz, 1H), 8.26 (s, 2H), 7.90 (dd, J=8.6, 1.8 Hz, 1H), 7.76 (ddd, J=8.2, 1.8 Hz, 1H), 7.65-7.55 (m, 3H), 7.37 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 7.24 (ddd, J=9.2, 2.2, 2.2 Hz, 2H), 4.69 (m, 2H), 4.54 (d, J=4.4 Hz, 2H), 4.47 (m, 2H). MS(ES+): m/z 467 (100) [MH+].

Workup

concentrationthe reaction mixture was concentrated in vacuo
custompurified by mass-directed purification

Sources & evidence

ORD record: ord-2fd1310a060c44429425360902c56702
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521448B2

Reaction notes

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