1-[({5'-chloro-4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl]oxy)methyl}cyclobutanecarboxylic acid → 1-[({5'-chloro-4-methyl-6'-[5-(trifluoromethyl)-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acid

HRID 623920Notes

Reaction equation

HRID 623920 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:25]2[CH:26]=[N:27][C:28]([O:32][CH2:33][C:34]3([C:38]([OH:40])=[O:39])[CH2:37][CH2:36][CH2:35]3)=[CH:29][C:30]=2[CH3:31])[CH:5]=[N:6][C:7]=1[C:8]1[N:9](COCC[Si](C)(C)C)[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=1>FC(F)(F)C(O)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:25]2[CH:26]=[N:27][C:28]([O:32][CH2:33][C:34]3([C:38]([OH:40])=[O:39])[CH2:35][CH2:36][CH2:37]3)=[CH:29][C:30]=2[CH3:31])[CH:5]=[N:6][C:7]=1[C:8]1[NH:12][C:11]([C:13]([F:14])([F:15])[F:16])=[CH:10][N:9]=1

Participants

4

Reactant 1

HCID 679753101-[({5'-chloro-4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl]oxy)methyl}cyclobutanecarboxylic acid

Product 1

HCID 680539781-[({5'-chloro-4-methyl-6'-[5-(trifluoromethyl)-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acidYield 61.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

In trifluoroacetic acid (3.1 mL) and water (0.3 mL) was dissolved 1-[({5′-chloro-4-methyl-6′-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl]oxy)methyl}cyclobutanecarboxylic acid (312 mg), and the mixture was allowed to stand at room temperature for 60 hours. The reaction mixture was concentrated under reduced pressure, subjected to azeotropic distillation with acetic acid, isopropyl ether was added to the obtained residue, and the precipitated solid was collected by filtration and dried under reduced pressure to obtain 1-[({5′-chloro-4-methyl-6′-[5-(trifluoromethyl)-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl}oxy)methyl]cyclobutanecarboxylic acid (151 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. distillationsubjected to azeotropic distillation with acetic acid, isopropyl ether
  3. additionwas added to the obtained residue
  4. filtrationthe precipitated solid was collected by filtration
  5. customdried under reduced pressure

Sources & evidence

ORD record
ord-e2735b48436044d3b3bc66583d581abc
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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