2-Fluoropyridine → 1-(4-{[3-(2-pyridyloxymethyl)cyclobutyl]oxy}phenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide

HRID 2111806Notes

Reaction equation

[OH:1][CH2:2][CH:3]1[CH2:6][CH:5]([O:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C:18]4[CH:19]=[CH:20][C:21]([C:23]([NH:25][CH2:26][C:27]5[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=5)=[O:24])=[CH:22][C:17]=4[N:16]=[CH:15]3)=[CH:10][CH:9]=2)[CH2:4]1.[H-].[Na+].F[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1>CN(C=O)C>[N:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[O:1][CH2:2][CH:3]1[CH2:4][CH:5]([O:7][C:8]2[CH:9]=[CH:10][C:11]([N:14]3[C:18]4[CH:19]=[CH:20][C:21]([C:23]([NH:25][CH2:26][C:27]5[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=5)=[O:24])=[CH:22][C:17]=4[N:16]=[CH:15]3)=[CH:12][CH:13]=2)[CH2:6]1

Participants

Conditions

Temperature: 60 °C

Procedure

1-(4-{[3-(Hydroxymethyl)cyclobutyl]oxy}phenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide (33 mg, 0.08 mmol) was dissolved in DMF and put under N2 atmosphere. Sodium hydride (2 mg, 0.08 mmol) was added and the reaction was heated to 60° C. 2-Fluoropyridine was then added and the reaction was then heated to 80° C. for 14 h. The reaction was cooled to rt and concentrated in vacuo. The crude solid was purified using the Waters mass-directed HPLC purification system to provide 1-(4-{[3-(2-pyridyloxymethyl)cyclobutyl]oxy}phenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide as an off-white solid. MS (ES+): m/z 507 (10) [MH+].

Workup

temperaturethe reaction was then heated to 80° C. for 14 h
temperatureThe reaction was cooled to rt
concentrationconcentrated in vacuo
customThe crude solid was purified
customthe Waters mass-directed HPLC purification system

Sources & evidence

ORD record: ord-4efb189824da4b4cbed172e71e69d083
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521448B2

Reaction notes

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