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

HRID 2203002Notes

Reaction equation

[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]4=[O:21])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[F:22][C:23]1[S:27][C:26]([CH2:28]O)=[CH:25][CH:24]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:28][C:26]5[S:27][C:23]([F:22])=[CH:24][CH:25]=5)=[CH:16][C:15]4=[O:21])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (127 mg), (5-fluorothiophen-2-yl)methanol (40 mg) and tributylphosphine (182 mg) in THF (15 ml) was added 1,1′-(azodicarbonyl)dipiperidine (227 mg), and the mixture was stirred at 60° C. for 4 h. The reaction mixture was then cooled to room temperature, and concentrated in vacuo. The residue was diluted with DCM, washed with water and brine successively, dried over Na2SO4, concentrated in vacuo and purified by column chromatography (MeOH/DCM) followed by preparative HPLC to afford the title compound (6 mg) as a white solid.

Workup

temperatureThe reaction mixture was then cooled to room temperature
concentrationconcentrated in vacuo
additionThe residue was diluted with DCM
washwashed with water and brine successively
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
custompurified by column chromatography (MeOH/DCM)

Sources & evidence

ORD record: ord-a9f36ae43fc049baa787f84f9f53945e
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365540B2

Reaction notes

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