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

HRID 2203066Notes

Reaction equation

HRID 2203066 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]([F:32])([F:31])[C:24]1[O:28][C:27]([CH2:29]O)=[CH:26][CH:25]=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][CH2:29][C:27]5[O:28][C:24]([C:23]([F:32])([F:31])[F:22])=[CH:25][CH:26]=5)=[CH:16][C:15]4=[O:21])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 7537667HCID 7537667, compoundHCID 896910841-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896910041-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((5-(trifluoromethyl)-2-furyl)methoxy)pyridin-2(1H)-oneYield 51.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (400 mg) and (5-(trifluoromethyl)-2-furyl)methanol (462 mg) in THF (40 ml) were added tributylphosphine (1.06 ml) and 1,1′-(azodicarbonyl)dipiperidine (1.08 g) at 60° C., and the mixture was stirred for 3 h. After the solvent was evaporated, the residue was purified by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by NH silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH). Then the resulting solid was recrystallized from EtOH-hexane to give the title compound (313 mg) as an off-white solid.

Workup

  1. customAfter the solvent was evaporated
  2. customthe residue was purified by silica gel column chromatography (hexane/EtOAc
  3. customThen the resulting solid was recrystallized from EtOH-hexane

Sources & evidence

ORD record
ord-b5bc97ea3aad40dbbff1739333a341e1
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

Loading…