Tributylphosphine → 1-(2-Ethyl-1-methyl-1H-benzimidazol-6-yl)-4-((5-fluorothiophen-2-yl)methoxy)pyridin-2(1H)-one

HRID 2203073Notes

Reaction equation

[CH2:1]([C:3]1[N:7]([CH3:8])[C:6]2[CH:9]=[C:10]([N:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:14]3=[O:20])[CH:11]=[CH:12][C:5]=2[N:4]=1)[CH3:2].[F:21][C:22]1[S:26][C:25]([CH2:27]O)=[CH:24][CH:23]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH2:1]([C:3]1[N:7]([CH3:8])[C:6]2[CH:9]=[C:10]([N:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:27][C:25]4[S:26][C:22]([F:21])=[CH:23][CH:24]=4)=[CH:15][C:14]3=[O:20])[CH:11]=[CH:12][C:5]=2[N:4]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (224 mg), (5-fluorothiophen-2-yl)methanol (100 mg) and tributylphosphine (750 mg) in THF (15 ml) was added 1,1′-(azodicarbonyl)dipiperidine (956 mg), and the mixture was stirred at 60° C. for 4 h. The reaction mixture was concentrated in vacuo, and diluted with DCM. The mixture was washed with water and brine successively, dried over Na2SO4, concentrated in vacuo and purified by silica gel column chromatography (MeOH/DCM) followed by preparative HPLC to afford the title compound (20 mg) as a white solid.

Workup

concentrationThe reaction mixture was concentrated in vacuo
additiondiluted with DCM
washThe mixture was washed with water and brine successively
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
custompurified by silica gel column chromatography (MeOH/DCM)

Sources & evidence

ORD record: ord-12a5d438ddc042259421d4d0e927d6e5
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365540B2

Reaction notes

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