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

HRID 2202937Notes

Reaction equation

HRID 2202937 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.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29]O)=[N:27][CH:28]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29][O:20][C:17]2[CH:18]=[CH:19][N:14]([C:11]3[CH:12]=[CH:13][C:6]4[N:5]=[C:4]([CH:1]5[CH2:2][CH2:3]5)[N:8]([CH3:9])[C:7]=4[CH:10]=3)[C:15](=[O:21])[CH:16]=2)=[N:27][CH:28]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 20537893(5-Chloropyridin-2-yl)methanolHCID 896910841-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896911444-((5-Chloropyridin-2-yl)methoxy)-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-oneYield 13.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (200 mg), (5-chloropyridin-2-yl)-methanol (152 mg) and tributylphosphine (437 mg) in THF (10 ml) was added 1,1′-(azodicarbonyl)dipiperidine (536 mg). The mixture was stirred under sonication at 50° C. for 3 h. The reaction mixture was then cooled to room temperature, and concentrated in vacuo. The residue was diluted with DCM (100 ml), washed with water and brine (30 ml), dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM) followed by preparative HPLC to give the title compound (40 mg) as a white solid.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with DCM (100 ml)
  4. washwashed with water and brine (30 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-8e6eba345673418b8908d339f483d14a
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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